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Intermittent subcutaneous exposure produces an osteoanabolic response by stimulating osteoblast activity and increasing bone formation. The molecule contains an α-aminoisobutyric-acid substitution and is distinct from endogenous PTHrP and from teriparatide. Regulatory authorization is product- and jurisdiction-specific: the FDA-approved TYMLOS label covers defined high-fracture-risk postmenopausal women and men, while the EMA-authorized ELADYNOS indication is for postmenopausal women at increased fracture risk.","evidenceQualitySummary":"The governed corpus includes the pivotal ACTIVE randomized phase 3 trial, histomorphometry and fracture analyses, the ACTIVExtend antiresorptive-sequencing study, trials in men and Japanese populations, a transdermal formulation trial, real-world comparative research, systematic reviews and network meta-analyses, and mechanistic or preclinical work. Source identities, titles, authorship, publication metadata, DOI/PMID links, peptide identity, and duplication were checked against PubMed. Evidence lanes and strength grades are provisional and preserve study-design boundaries; detailed claim-level risk-of-bias, applicability, and contradiction review remains part of accountable Owner review.","safetyConcernsSummary":"Most fracture-outcome evidence comes from selected trial populations, especially postmenopausal women, and may not generalize to every patient with osteoporosis. Some studies use bone-mineral density or bone-turnover markers rather than fracture endpoints; indirect comparisons cannot replace adequately powered head-to-head trials. Sponsorship, formulation differences, adherence, background calcium or vitamin D, subsequent antiresorptive therapy, renal function, baseline fracture risk, and jurisdictional labeling affect interpretation. Long-duration human data are limited; rare risks and postmarketing events cannot be fully characterized by preauthorization trials. Current product labeling—not this profile—controls contraindications, warnings, duration, and clinical use.","archiveSummaryNote":"Across the randomized evidence, daily subcutaneous abaloparatide increased bone-mineral-density measures and reduced new vertebral fractures in postmenopausal women compared with placebo; follow-on alendronate research indicates that antiresorptive treatment can help maintain gains after an anabolic course. Evidence in men supports increased bone density, but fracture-outcome evidence is less mature than in postmenopausal women. Comparative and network-meta-analytic findings help place abaloparatide among anabolic osteoporosis therapies but inherit heterogeneity and indirect-comparison limitations. 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Then, confronted with obstructed vessels, there is circumvention of the occlusion, which may be the particular action of BPC 157 in ische …","authors":"Seiwerth S, Milavic M, Vukojevic J, Gojkovic S, Krezic I, Vuletic LB, Pavlov KH, Petrovic A, Sikiric S, Vranes H, Prtoric A, Zizek H, Durasin T, Dobric I, Staresinic M, Strbe S, Knezevic M, Sola M, Kokot A, Sever M, Lovric E, Skrtic A, Blagaic AB, Sikiric P.","publishingOrg":null,"publicationYear":2021,"doi":"10.3389/fphar.2021.627533","pubmedId":"34267654","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. 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Its N-terminal D-phenylalanine-containing sequence binds the catalytic site of thrombin while a C-terminal region engages thrombin’s fibrin-recognition exosite; thrombin can subsequently cleave the molecule, contributing to reversible inhibition. It acts directly on circulating and clot-bound thrombin without requiring antithrombin. The molecule is established in percutaneous coronary intervention, while use in extracorporeal membrane oxygenation, cardiopulmonary bypass, pediatric procedures, and other settings has a different and often off-label evidence and regulatory context.","evidenceQualitySummary":"The governed corpus spans the pivotal REPLACE-2, ACUITY, HORIZONS-AMI, EUROMAX, HEAT-PPCI, MATRIX, VALIDATE-SWEDEHEART, and BRIGHT-4 evidence families; post-procedure infusion research; early angioplasty studies; pediatric catheterization and ECMO investigations; modern systematic reviews and individual-patient or aggregate meta-analyses; laboratory monitoring research; and comparative real-world work. Source identities, titles, authorship, publication metadata, DOI/PMID links, bivalirudin identity, and duplication were checked against PubMed. Evidence ratings preserve differences among large PCI trials, pediatric pilot studies, ECMO cohorts, meta-analyses, and in-vitro assays. Claim-level interpretation, bias, applicability, and changing background antiplatelet or access-site practice remain for accountable Owner review.","safetyConcernsSummary":"The evidence base spans two decades of changing PCI technique, radial-access adoption, antiplatelet therapy, heparin dosing, glycoprotein IIb/IIIa use, and stent technology, limiting direct comparison across trials. Open-label designs and treatment crossovers occur in parts of the literature. Composite outcomes and bleeding definitions vary. Meta-analyses inherit comparator heterogeneity and cannot erase trial-level differences. Evidence for ECMO, cardiopulmonary bypass, neurointervention, and children is smaller and often observational. Renal clearance, critical illness, assay limitations, extracorporeal-circuit conditions, and concomitant antithrombotic drugs affect exposure and bleeding or thrombosis risk. Current official labeling—not this profile—controls indications, contraindications, monitoring, and clinical use.","archiveSummaryNote":"Randomized PCI trials establish that bivalirudin is an effective procedural anticoagulant, but its balance against heparin depends on the comparator regimen, glycoprotein IIb/IIIa inhibitor strategy, vascular access, post-PCI infusion, ischemic-risk profile, and era of practice. Across major trial programs, reduced bleeding in some comparisons must be considered alongside acute stent-thrombosis signals and differences in ischemic outcomes. Later evidence, including BRIGHT-4 and pooled analyses, evaluates whether high-dose post-PCI infusion and contemporary practice alter that balance. ECMO, cardiopulmonary-bypass, pediatric, and HIT-associated uses are clinically important but supported by smaller, heterogeneous, and frequently nonrandomized evidence; they are not interchangeable with the FDA PCI indication. Monitoring research also shows that assay choice and patient physiology can affect interpretation of anticoagulant effect.","openQuestionsText":"Which contemporary PCI populations derive a net clinical advantage from bivalirudin over modern heparin strategies? What infusion duration and intensity best balance bleeding and acute stent thrombosis after primary PCI? Which anticoagulation assay most reliably reflects exposure in ECMO, renal dysfunction, and critical illness? Can adequately powered randomized trials define outcomes in adult and pediatric ECMO or cardiopulmonary bypass? How should HIT history, circuit adsorption, inflammatory state, organ failure, and concurrent antiplatelet therapy change interpretation? 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Three groups of 1-wk-old GHRHKO mice were treated for 5 wk with 2 microg of CJC-1295 at intervals of 24, 48, and 72 h. ...These findings demonstrate that treatment with once-daily admi …","authors":"Alba M, Fintini D, Sagazio A, Lawrence B, Castaigne JP, Frohman LA, Salvatori R.","publishingOrg":null,"publicationYear":2006,"doi":"10.1152/ajpendo.00201.2006","pubmedId":"16822960","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. 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Relationship to named compound is explicitly classified.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes mechanistic evidence concerning Peptide Supplements and Their Therapeutic Applications in Sports Medicine.","supportNature":"contextualizes","qualification":"Compound-specific evidence is preclinical, mechanistic, or otherwise insufficient to establish human clinical efficacy or safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-eight-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1177/03635465261464420","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T19:33:45.384Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:cjc-1295:wave2:2026-09-08","evidenceLane":"mechanistic","extractionPayload":{"limitations":["Compound-specific evidence is preclinical, mechanistic, or otherwise insufficient to establish human clinical efficacy or safety."],"studyDesign":"Mechanistic or contextual peer-reviewed report","sourceStrength":{"note":"Automated structured-metadata baseline; full-text risk-of-bias review may revise this rating.","grade":"C","score":63,"version":"WPF-ESR-1.0","dimensions":{"authority":78,"reporting":68,"directness":88,"replication":72,"designAndBias":42,"populationRelevance":30},"provisional":true},"directCompoundEvidence":true,"relationshipToNamedCompound":"direct_compound"},"provenancePayload":{"doi":"10.1177/03635465261464420","pmid":"42578445","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"relationshipClassified":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T19:33:45.384Z","updatedAt":"2026-09-08T19:33:45.384Z"},{"id":"3d778a34d95451d0a9ac1db3d863b295","peptideId":"b6eac7dd-9ae2-4b2c-86e8-0ba95f48c9ee","title":"Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/19386527/","evidenceTier":"laboratory","summary":"Serum GH and IGF-1 levels have been shown to increase with administration of GHRH or CJC-1295, a long-acting GHRH analog. DESIGN: Sera from 11 healthy young adult men before and one week after CJC-1295 injection were analyze …","authors":"Sackmann-Sala L, Ding J, Frohman LA, Kopchick JJ.","publishingOrg":null,"publicationYear":2009,"doi":"10.1016/j.ghir.2009.03.001","pubmedId":"19386527","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. 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Structural changes—including a thioether bridge and O-methyltyrosine substitution—slow enzymatic degradation relative to oxytocin. In obstetric use it stimulates uterine smooth-muscle contraction after delivery; authorization, route, dose, and eligible population remain product- and jurisdiction-specific. Intranasal developmental research in Prader–Willi syndrome is a distinct investigational context and is not evidence of an obstetric product’s authorization for that use.","evidenceQualitySummary":"The governed corpus contains the large heat-stable-carbetocin vaginal-birth trial, randomized cesarean and vaginal-delivery comparisons, dose and cardiovascular-safety studies, high- and low-risk subgroup syntheses, Cochrane and network meta-analyses, and a separately labeled Prader–Willi trial. All 25 source identities, titles, authorship, publication metadata, DOI/PMID links, molecule relevance, active status, and duplication were checked against PubMed. Evidence grading remains provisional pending Owner review, and meta-analyses are not treated as independent replications of their component trials.","safetyConcernsSummary":"Trials vary in postpartum-haemorrhage thresholds, cesarean urgency, uterotonic regimens, anaesthetic context, and ascertainment of nausea, hypotension, tachycardia, myocardial markers, and other adverse effects. Rare harms and uncommon high-risk obstetric situations are not fully resolved by existing trials. Results from heat-stable formulations or one administration route may not transfer to another. Current regulated labeling and obstetric protocols—not this profile—control contraindications, monitoring, and use.","archiveSummaryNote":"Across obstetric trials, prophylactic carbetocin has been compared chiefly with oxytocin and other uterotonics for postpartum-haemorrhage prevention and need for additional uterotonics. Results depend on delivery route, baseline haemorrhage risk, comparator dose and stability, outcome definition, and care setting. The archive separately represents efficacy, adverse effects, cardiac-repolarization/troponin research, heat-stable formulation evidence, and the non-obstetric intranasal research program. It does not collapse those indications or formulations into one claim.","openQuestionsText":"Which women and delivery settings obtain a clinically meaningful advantage over appropriately stored oxytocin? How do heat-stable products perform across low-resource health systems under routine conditions? What dosing best balances uterine effect and cardiovascular adverse events in high-risk cesarean delivery? Which postpartum-haemorrhage definitions and core outcomes should future trials share? Do pharmacogenomic or receptor-level differences predict response? 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In particular, Epitalon increases the lifespan of mice and fruit flies and restores the circadian rhythms of melatonin and cortisol production in old rhesus monkeys …","authors":"Khavinson VKh.","publishingOrg":null,"publicationYear":2002,"doi":null,"pubmedId":"12374906","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. 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It binds copper and has been studied in copper handling, extracellular-matrix remodeling, fibroblast activity, inflammatory signaling, antioxidant responses, and wound repair. Effects are formulation-, concentration-, route-, and model-dependent.","evidenceQualitySummary":"The archive is rich in biochemical, cell, gene-expression, and animal work but sparse in rigorous human trials. Small or incompletely reported topical cosmetic studies provide signals, not proof. Preclinical findings do not validate injectable, systemic, anti-aging, hair-growth, or disease-treatment claims.","safetyConcernsSummary":"Topical cosmetic use does not establish the safety of compounded, injected, intranasal, or systemic GHK-Cu. Purity, copper content, sterility, dose, route, local reactions, sensitization, systemic copper exposure, interactions, and long-term safety remain important uncertainties.","archiveSummaryNote":"Governed corpus covering chemical identity, discovery, copper-binding mechanisms, skin-regeneration synthesis, gene-expression hypotheses, and animal wound models, with evidence lanes kept separate.","openQuestionsText":"Independent randomized human trials; standardized formulations; dose-response and tissue pharmacokinetics; long-term topical safety; systemic or injectable safety; reproducibility of gene-expression claims; and meaningful wound, skin, or hair outcomes.","active":true,"createdAt":"2026-08-18T17:25:09.603Z","updatedAt":"2026-09-09T00:26:17.447Z","entityClass":"peptide_conjugate","entityClassSource":"human_reviewed","entityClassReviewed":true,"entityClassReviewedBy":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","entityClassReviewedAt":"2026-09-09T00:26:17.447Z","registryStatus":"canonical","registryTier":null,"acquisitionEnabled":true,"publicationState":"published","editorialState":"published","chemistry":{"id":"572dbd18d0b617edd3c1ede869d10e14","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","molecularFormula":"C14H22CuN6O4","molecularWeight":401.91,"aminoAcidSequence":"Gly-His-Lys","smiles":"C1=C(NC=N1)CC(C(=O)NC(CCCCN)C(=O)O)NC(=O)CN.[Cu]","inchi":"1S/C14H24N6O4.Cu/c15-4-2-1-3-10(14(23)24)20-13(22)11(19-12(21)6-16)5-9-7-17-8-18-9;/h7-8,10-11H,1-6,15-16H2,(H,17,18)(H,19,21)(H,20,22)(H,23,24);","inchikey":"DIWZQABMLHSNJR-UHFFFAOYSA-N","structureImageUrl":"https://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?cid=378611&t=l","createdAt":"2026-09-08T18:31:47.338Z","updatedAt":"2026-09-08T18:31:47.338Z"},"citations":[{"id":"8fed56b6668438829860683f89502221","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) Attenuates CuSO4 or LPS induced-inflammation in Zebrafish larvae model.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/41997403/","evidenceTier":"animal","summary":"Inflammation serves as a basic defense mechanism against both internal and external threats, while the unresolved or excessive inflammation can lead to irreversible tissue damage. Glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu), a bioactive tripeptide complex known for its anti-aging and tissue repair properties, is extensively utilized in dermatological and hair care formulations. However, the role of GHK-Cu in regulating inflammation is less known. In this study, we explored the anti-inflammatory effects of GHK-Cu against the acute inflammation induced by copper sulfate (CuSO4) and lipopolysaccharide (LPS) in zebrafish larvae. GHK-Cu notably decreased the migration of neutrophils and...","authors":"Jing Hu, Chao Zhang, Feifei Wang","publishingOrg":null,"publicationYear":2026,"doi":"10.1016/j.ejphar.2026.178880","pubmedId":"41997403","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning Glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) Attenuates CuSO4 or LPS induced-inflammation in Zebrafish larvae model.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/j.ejphar.2026.178880","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article"]},"provenancePayload":{"doi":"10.1016/j.ejphar.2026.178880","pmid":"41997403","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"6f128665d6d60f44cc4ff985650df5c5","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/3169264/","evidenceTier":"laboratory","summary":"Glycyl-L-histidyl-L-lysine (GHK) is a tripeptide with affinity for copper(II) ions and was isolated from human plasma. This peptide appears to play a physiological role in wound healing. We report the stimulating effect of GHK-Cu on collagen synthesis by fibroblasts. The stimulation began between 10(-12) and 10(-11) M, maximized at 10(-9) M, and was independent of any change in cell number. The presence of a GHK triplet in the alpha 2(I) chain of type I collagen suggests that the tripeptide might be liberated by proteases at the site of a wound and exert in situ healing effects.","authors":"F X Maquart, L Pickart, M Laurent, P Gillery, J C Monboisse, J P Borel","publishingOrg":null,"publicationYear":1988,"doi":"10.1016/0014-5793(88)80509-x","pubmedId":"3169264","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes in_vitro evidence concerning Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/0014-5793(88)80509-x","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"in_vitro","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1016/0014-5793(88)80509-x","pmid":"3169264","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"a11907a4cb53722057ab85df36013493","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/8227353/","evidenceTier":"animal","summary":"The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) was first described as a growth factor for differentiated cells. Recent in vitro data showed that it possesses several properties of a potential activator of wound repair. We investigated the effects of GHK-Cu in vivo, using the wound chamber model described previously (Schilling, J.A., W. Joel, and M.T. Shurley, 1959. Surgery [St. Louis]. 46:702-710). Stainless steel wire mesh cylinders were implanted subcutaneously on the back of rats. The animals were divided into groups that received sequential injections into the wound chamber of either saline (control group) or various concentrations of GHK-Cu. At the end of the...","authors":"F X Maquart, G Bellon, B Chaqour, J Wegrowski, L M Patt, R E Trachy, J C Monboisse, F Chastang","publishingOrg":null,"publicationYear":1993,"doi":"10.1172/JCI116842","pubmedId":"8227353","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1172/jci116842","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1172/JCI116842","pmid":"8227353","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"e22a7cef2859bde1111dcdc1e97b72f4","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Are We Ready to Measure Skin Permeation of Modern Antiaging GHK-Cu Tripeptide Encapsulated in Liposomes?","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/39795193/","evidenceTier":"insufficient","summary":"Cosmetically active compounds (CACs), both of lipophilic and hydrophilic origin, have difficulty reaching the deeper layers of the skin, and this shortcoming significantly reduces their efficacy. One such CAC that occurs naturally in the human body and displays many beneficial properties (via reducing fine lines and wrinkles, tightening skin, improving its elasticity, etc.) is the glycyl-L-histidyl-L-lysine tripeptide complex of copper (GHK-Cu). GHK-Cu is a fairly hydrophilic compound with limited permeation through the lipophilic stratum corneum. On the other hand, liposomes capable of encapsulating GHK-Cu may improve its permeation potential. The present review discusses various issues...","authors":"Karolina Ogórek, Kinga Nowak, Emilia Wadych, Lena Ruzik, Andrei R Timerbaev, Magdalena Matczuk","publishingOrg":null,"publicationYear":2025,"doi":"10.3390/molecules30010136","pubmedId":"39795193","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Are We Ready to Measure Skin Permeation of Modern Antiaging GHK-Cu Tripeptide Encapsulated in Liposomes?","supportNature":"contextualizes","qualification":"Narrative synthesis; conclusions depend on source selection and do not substitute for primary clinical evidence.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.3390/molecules30010136","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Narrative synthesis; conclusions depend on source selection and do not substitute for primary clinical evidence."],"studyDesign":"Narrative review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.3390/molecules30010136","pmid":"39795193","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"018c4a95b63fc613ab1decff73f12184","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"The human tri-peptide GHK and tissue remodeling.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/18644225/","evidenceTier":"insufficient","summary":"Tissue remodeling follows the initial phase of wound healing and stops inflammatory and scar-forming processes, then restores the normal tissue morphology. The human peptide Gly-(L-His)-(L-Lys) or GHK, has a copper 2+ (Cu(2+)) affinity similar to the copper transport site on albumin and forms GHK-Cu, a complex with Cu(2+). These two molecules activate a plethora of remodeling related processes: (1) chemoattraction of repair cells such as macrophages, mast cells, capillary cells; (2) anti-inflammatory actions (suppression of free radicals, thromboxane formation, release of oxidizing iron, transforming growth factor beta-1, tumor necrosis factor alpha and protein glycation while increasing...","authors":"Loren Pickart","publishingOrg":null,"publicationYear":2008,"doi":"10.1163/156856208784909435","pubmedId":"18644225","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning The human tri-peptide GHK and tissue remodeling.","supportNature":"contextualizes","qualification":"Narrative synthesis; conclusions depend on source selection and do not substitute for primary clinical evidence.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1163/156856208784909435","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Narrative synthesis; conclusions depend on source selection and do not substitute for primary clinical evidence."],"studyDesign":"Narrative review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.1163/156856208784909435","pmid":"18644225","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"0b4df9e41db519edac8425100a2e57bc","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"ESI-MS study of the mechanism of glycyl-l-histidyl-l-lysine-Cu(II) complex transport through model membrane of stratum corneum.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/19071668/","evidenceTier":"laboratory","summary":"In mammalian organisms copper can be found mainly in the form of complex with specific tripeptide, GHK-Cu (glycyl-l-histidyl-l-lysine-Cu(II)). GHK-Cu is the basic form in which copper is transported in tissues and permeates through cell membranes. The penetration ability of GHK-Cu through the stratum corneum and its role in copper ions transport process is the key issue for its cosmetic and pharmaceutical activity. The permeability phenomenon was studied by use in vitro model system-Flynn diffusion cell with the liposome membrane. The earlier studies on the influence of different ligands on the migration rate of copper ions through model membrane provide evidence for hampering role of...","authors":"Lena Mazurowska, Mirosław Mojski","publishingOrg":null,"publicationYear":2007,"doi":"10.1016/j.talanta.2006.11.034","pubmedId":"19071668","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes in_vitro evidence concerning ESI-MS study of the mechanism of glycyl-l-histidyl-l-lysine-Cu(II) complex transport through model membrane of stratum corneum.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/j.talanta.2006.11.034","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"in_vitro","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article"]},"provenancePayload":{"doi":"10.1016/j.talanta.2006.11.034","pmid":"19071668","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"bb2acf44ef7046b57e20f02b84ef1477","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging: implications for cognitive health.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/22666519/","evidenceTier":"insufficient","summary":"Oxidative stress, disrupted copper homeostasis, and neuroinflammation due to overproduction of proinflammatory cytokines are considered leading causative factors in development of age-associated neurodegenerative conditions. Recently, a new mechanism of aging-detrimental epigenetic modifications-has emerged. Thus, compounds that possess antioxidant, anti-inflammatory activity as well as compounds capable of restoring copper balance and proper gene functioning may be able to prevent age-associated cognitive decline and ward off many common neurodegenerative conditions. The aim of this paper is to bring attention to a compound with a long history of safe use in wound healing and antiaging...","authors":"Loren Pickart, Jessica Michelle Vasquez-Soltero, Anna Margolina","publishingOrg":null,"publicationYear":2012,"doi":"10.1155/2012/324832","pubmedId":"22666519","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging: implications for cognitive health.","supportNature":"contextualizes","qualification":"Narrative synthesis; conclusions depend on source selection and do not substitute for primary clinical evidence.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1155/2012/324832","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Narrative synthesis; conclusions depend on source selection and do not substitute for primary clinical evidence."],"studyDesign":"Narrative review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.1155/2012/324832","pmid":"22666519","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"791d177debf88ec3419bbf085051a344","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+).","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/11121126/","evidenceTier":"animal","summary":"Glycyl-histidyl-lysine-Cu(2+) is a tripeptide-copper complex previously shown to be an activator of wound healing. We have investigated the effects of glycyl-histidyl-lysine-Cu(2+) on the synthesis of glycosaminoglycans and small proteoglycans in a model of rat experimental wounds and in rat dermal fibroblast cultures. Repeated injections of glycyl-histidyl-lysine-Cu(2+) (2 mg per injection) stimulated the wound tissue production, as appreciated by dry weight and total protein measurements. This stimulation was accompanied by an increased production of type I collagen and glycosaminoglycans (assessed, respectively, by hydroxyproline and uronic acid contents of the chamber)....","authors":"A Siméon, Y Wegrowski, Y Bontemps, F X Maquart","publishingOrg":null,"publicationYear":2000,"doi":"10.1046/j.1523-1747.2000.00166.x","pubmedId":"11121126","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+).","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1046/j.1523-1747.2000.00166.x","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1046/j.1523-1747.2000.00166.x","pmid":"11121126","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"889187d2ab32569209d90428af1debe6","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Copper-tripeptides (cuzymes) with peroxidase-mimetic activity.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/35515638/","evidenceTier":"laboratory","summary":"Peroxidases are enzymes that use hydrogen peroxide to oxidize substrates such as 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ATBS). In this study, we showed that copper-tripeptide complexes (\"cuzymes\") also exhibited peroxidase-like activities. Different cuzymes could be formed by using various tripeptide ligands, such as GGG, GGH or HGG. However, the peroxidase-like activity of cuzymes depends on the sequence of the tripeptide (Cu-GGG > Cu-HGG > Cu-GGH). When ABTS was used as the substrate, the activity of Cu-GGG was 326 ± 1.5 U mg-1 which was 2.5 times higher than that of horseradish peroxidase (HRP). Copper-tripeptide complexes were also used to degrade trypan blue dye. By...","authors":"Le Truc Nguyen, Wing Fat Ho, Kun-Lin Yang","publishingOrg":null,"publicationYear":2020,"doi":"10.1039/d0ra02472d","pubmedId":"35515638","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes mechanistic evidence concerning Copper-tripeptides (cuzymes) with peroxidase-mimetic activity.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1039/d0ra02472d","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"mechanistic","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article"]},"provenancePayload":{"doi":"10.1039/d0ra02472d","pmid":"35515638","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"a7da463aaf3c15d5ac1d89931930d3fb","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Relief of ovalbumin-induced airway remodeling by the glycyl-l-histidyl-l-lysine-Cu2+ tripeptide complex via activation of SIRT1 in airway epithelial cells.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/37257226/","evidenceTier":"animal","summary":"Fixed airflow limitation (FAO), prevalent in patients with severe or difficult-to-treat asthma, is mainly caused by airway remodeling. Airway remodeling is initiated by inflammation and involves subsequent pathological changes. Glycyl-l-histidyl-l-lysine (GHK) is a matrikine with anti-inflammatory and antioxidant effects, naturally existing in human tissue. At present, the GHK level in human plasma and whether it is related to airway remodeling of asthma remain unclear. This study was conducted to determine how GHK is involved in airway remodeling in asthma. Our result showed that the plasma GHK levels of patients with asthma were significantly lower than those of age-matched healthy...","authors":"Qin Zhang, Jia Liu, Ming-Ming Deng, Run Tong, Gang Hou","publishingOrg":null,"publicationYear":2023,"doi":"10.1016/j.biopha.2023.114936","pubmedId":"37257226","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning Relief of ovalbumin-induced airway remodeling by the glycyl-l-histidyl-l-lysine-Cu2+ tripeptide complex via activation of SIRT1 in airway epithelial cells.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/j.biopha.2023.114936","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article"]},"provenancePayload":{"doi":"10.1016/j.biopha.2023.114936","pmid":"37257226","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"564ab51be5206b0b816a4cec80a3b067","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/1522753/","evidenceTier":"laboratory","summary":"Glycyl-L-histidyl-L-lysine-copper (II) complex (GHK-Cu) is a naturally occurring tripeptide with potential healing properties. We studied the effect of GHK-Cu on the synthesis of glycosaminoglycans (GAGs) by normal human fibroblasts in culture. Cells were incubated with 3H glucosamine and 35S sulfate and the radioactivity of isolated GAGs was determined. GHK-Cu induced a dose-dependent increase of the synthesis of total GAGs secreted into the culture medium and those associated with the cell layer. The effect of GHK-Cu was biphasic with a maximal stimulation at 10(-9) to 10(-8) M. At higher concentrations, the rate of synthesis returned progressively to that of control cultures....","authors":"Y Wegrowski, F X Maquart, J P Borel","publishingOrg":null,"publicationYear":1992,"doi":"10.1016/0024-3205(92)90504-i","pubmedId":"1522753","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes in_vitro evidence concerning Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/0024-3205(92)90504-i","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"in_vitro","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1016/0024-3205(92)90504-i","pmid":"1522753","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"de8ea06a5505868f17ddafa70ae72c90","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Copper Complexes with New Glycyl-l-histidyl-l-lysine-Hyaluronan Conjugates Show Antioxidant Properties and Osteogenic and Angiogenic Synergistic Effects.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/40123442/","evidenceTier":"laboratory","summary":"In recent years, hyaluronic acid (HA) and the natural tripeptide glycyl-l-histidyl-l-lysine (GHK), especially its copper(II) complex (GHK-Cu), individually have been shown to exert helpful properties for bone protection and regeneration. However, they are not strong enough to handle oxidative stress, hydrolytic attack, or environmental conditions. Being aware that conjugation chemistry has recently emerged as an appealing approach for generating new molecular entities capable of preserving the molecular integrity of their moieties or delaying their degradation, herein we present the synthesis of conjugates of HA with GHK (GHK-HA), at different loadings of the tripeptide. GHK-HA binds...","authors":"Valentina Greco, Valeria Lanza, Barbara Tomasello, Irina Naletova, Warren R L Cairns, Sebastiano Sciuto, Enrico Rizzarelli","publishingOrg":null,"publicationYear":2025,"doi":"10.1021/acs.bioconjchem.4c00545","pubmedId":"40123442","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes in_vitro evidence concerning Copper Complexes with New Glycyl-l-histidyl-l-lysine-Hyaluronan Conjugates Show Antioxidant Properties and Osteogenic and Angiogenic Synergistic Effects.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1021/acs.bioconjchem.4c00545","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"in_vitro","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1021/acs.bioconjchem.4c00545","pmid":"40123442","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"75af817fa2f417a0b77ed69275340668","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Glycyl-L-histidyl-L-lysine-Cu2+ attenuates cigarette smoke-induced pulmonary emphysema and inflammation by reducing oxidative stress pathway.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/35936787/","evidenceTier":"animal","summary":"Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder manifested as chronic airway inflammation and persistent airflow limitation with the essential mechanism as inflammatory response and oxidative stress induced by toxic exposures such as cigarette smoke (CS). Glycyl-L-histidyl-L-lysine (GHK) is a nontoxic tripeptide involved in the process of healing and regeneration as a natural product. With the combination of Cu(II), glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) improves antioxidative and anti-inflammatory bioavailability, and they might offer potential therapeutic properties for COPD. Thus, the present study aimed to identify the potential effects of...","authors":"Qin Zhang, Liming Yan, Jingwen Lu, Xiaoming Zhou","publishingOrg":null,"publicationYear":2022,"doi":"10.3389/fmolb.2022.925700","pubmedId":"35936787","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning Glycyl-L-histidyl-L-lysine-Cu2+ attenuates cigarette smoke-induced pulmonary emphysema and inflammation by reducing oxidative stress pathway.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.3389/fmolb.2022.925700","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article"]},"provenancePayload":{"doi":"10.3389/fmolb.2022.925700","pmid":"35936787","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"8977b6e22427fc70f24a3fb47f4e71b2","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Effects of the tripeptide glycyl-L-histidyl-L-lysine copper complex on osteoblastic cell spreading, attachment and phenotype.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/8747089/","evidenceTier":"animal","summary":"We have studied the effects of the complex Glycyl-L-Histidyl-L-Lysine:Cu (GHK:Cu), the GHK sequence present in the alpha 2 (I) chain of human collagen (Coll I), and bone matrix glycoproteins containing either RGD (fibronectin, FN), or RGD and GHK (Coll I), on the spreading, attachment and markers of the osteoblast phenotype in rat calvaria cells (RC), human trabecular osteoblastic cells (HT) and human marrow stromal cells (HM). Coll I (20 micrograms/ml) and FN (20 micrograms/ml) coating enhanced osteoblastic cell spreading, whereas free GHK:Cu and GHK coating (10(-10)-10(-8) M) had no effect. FN and Coll I, as well as GHK:Cu and GHK, increased the attachment of RC and HT cells. The...","authors":"D Godet, P J Marie","publishingOrg":null,"publicationYear":1995,"doi":null,"pubmedId":"8747089","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning Effects of the tripeptide glycyl-L-histidyl-L-lysine copper complex on osteoblastic cell spreading, attachment and phenotype.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"pmid:8747089","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"C","score":60,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article"]},"provenancePayload":{"doi":null,"pmid":"8747089","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"a79b11641d083baf4f5aa5ca27ded5d5","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/11045606/","evidenceTier":"animal","summary":"Glycyl-histidyl-lysine-Cu2+ (GHK-Cu) is a tripeptide-copper complex known to be a potent wound healing agent. We previously showed its ability to stimulate in vitro and in vivo the synthesis of extracellular matrix components. The aim of this study was to determine the effects of GHK-Cu on MMP-2 synthesis by dermal fibroblasts in culture. We showed that GHK-Cu increased MMP-2 levels in conditioned media of cultured fibroblasts. This effect was reproduced by copper ions but not by the tripeptide GHK alone. This stimulation was accompanied by an increase of MMP-2 mRNA level. We also showed that GHK-Cu increased the secretion of the tissue inhibitors of metalloproteinases, TIMP-1 and...","authors":"A Siméon, H Emonard, W Hornebeck, F X Maquart","publishingOrg":null,"publicationYear":2000,"doi":"10.1016/s0024-3205(00)00803-1","pubmedId":"11045606","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/s0024-3205(00)00803-1","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1016/s0024-3205(00)00803-1","pmid":"11045606","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"26125691eb3361cd87163bb8221a5787","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Topically applied GHK as an anti-wrinkle peptide: Advantages, problems and prospective.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/39963574/","evidenceTier":"insufficient","summary":"Peptides are promising and attractive anti-wrinkle active ingredients, amongst which glycyl-histidyl-lysine peptide (GHK) is one of the most broadly promoted peptide for topical application. This simple sequence of amino acid residues not only has the capability of tissue regeneration and the enhancement of collagen and glycosaminoglycans synthesis but also is able to increase nerve outgrowth and angiogenesis. Consequently, GHK has several properties, from wound healing to prevention/reduction wrinkles. GHK-Cu and Pal-GHK are metal complex and palmitoylated derivatives of GHK, respectively. Although GHK-Cu and Pal-GHK are widely used in anti-wrinkle products available on the cosmetic...","authors":"Seyedeh Maryam Mortazavi, Seyyed Ali Mohammadi Vadoud, Hamid Reza Moghimi","publishingOrg":null,"publicationYear":2025,"doi":"10.34172/bi.30071","pubmedId":"39963574","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Topically applied GHK as an anti-wrinkle peptide: Advantages, problems and prospective.","supportNature":"contextualizes","qualification":"Narrative synthesis; conclusions depend on source selection and do not substitute for primary clinical evidence.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.34172/bi.30071","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Narrative synthesis; conclusions depend on source selection and do not substitute for primary clinical evidence."],"studyDesign":"Narrative review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.34172/bi.30071","pmid":"39963574","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"1ed2ddcc2e34afd9f08ad306960f2f4f","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Glycyl-l-histidyl-l-lysine-Cu2+ rescues cigarette smoking-induced skeletal muscle dysfunction via a sirtuin 1-dependent pathway.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/36905132/","evidenceTier":"animal","summary":"Skeletal muscle dysfunction is an important co-morbidity in patients with chronic obstructive pulmonary disease (COPD) and is significantly associated with increased mortality. Oxidative stress has been demonstrated an important trigger for COPD-related skeletal muscle dysfunction. Glycine-histidine-lysine (GHK) is an active tripeptide, which is a normal component of human plasma, saliva, and urine; promotes tissue regeneration; and acts as an anti-inflammatory and antioxidant properties. The purpose of this study was to determine whether GHK is involved in COPD-related skeletal muscle dysfunction. The plasma GHK level in patients with COPD (n = 9) and age-paired healthy subjects (n =...","authors":"Mingming Deng, Qin Zhang, Liming Yan, Yiding Bian, Ruixia Li, Jinghan Gao, Yingxi Wang, Jinrui Miao","publishingOrg":null,"publicationYear":2023,"doi":"10.1002/jcsm.13213","pubmedId":"36905132","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning Glycyl-l-histidyl-l-lysine-Cu2+ rescues cigarette smoking-induced skeletal muscle dysfunction via a sirtuin 1-dependent pathway.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1002/jcsm.13213","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1002/jcsm.13213","pmid":"36905132","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"b4f3d19ac829882734dd9bc92462b3ee","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"The glycyl-l-histidyl-l-lysine-Cu2+ tripeptide complex attenuates lung inflammation and fibrosis in silicosis by targeting peroxiredoxin 6.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/38879894/","evidenceTier":"animal","summary":"Silicosis is the most common type of pneumoconiosis, having a high incidence in workers chronically exposed to crystalline silica (CS). No specific medication exists for this condition. GHK, a tripeptide naturally occurring in human blood and urine, has antioxidant effects. We aimed to investigate the therapeutic effect of GHK-Cu on silicosis and its potential underlying molecular mechanism. An experimental silicosis mouse model was established to observe the effects of GHK-Cu on lung inflammation and fibrosis. Moreover, the effects of GHK-Cu on the alveolar macrophages (AM) were examined using the RAW264.7 cell line. Its molecular target, peroxiredoxin 6 (PRDX6), has been identified,...","authors":"Yiding Bian, Mingming Deng, Jia Liu, Jiaye Li, Qin Zhang, Zilin Wang, Liwei Liao, Jinrui Miao","publishingOrg":null,"publicationYear":2024,"doi":"10.1016/j.redox.2024.103237","pubmedId":"38879894","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning The glycyl-l-histidyl-l-lysine-Cu2+ tripeptide complex attenuates lung inflammation and fibrosis in silicosis by targeting peroxiredoxin 6.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/j.redox.2024.103237","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article"]},"provenancePayload":{"doi":"10.1016/j.redox.2024.103237","pmid":"38879894","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"7efa3539dea6d6ff62d881f94db05f16","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"The potential of GHK as an anti-aging peptide.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/35083444/","evidenceTier":"animal","summary":"GHK (glycyl-L-histidyl-L-lysine) is a naturally occurring peptide found in human serum with levels averaging 200 ng/ml at age 20 but declining to an average of 80 ng/ml by age 60. The molecule has a very high affinity for copper and forms the chelate GHK-Cu. The peptide as well as its Cu (II) chelate have anti-inflammatory and tissue remodeling properties. GHK-Cu has been shown to promote skin remodeling, wound healing and regeneration, and has prominent antioxidant and anti-inflammatory effects in in vitro and in vivo studies. In addition, preliminary observations suggest GHK can partially reverse cognitive impairment in aging mice by targeting anti-inflammatory and epigenetic pathways....","authors":"Yan Dou, Amanda Lee, Lida Zhu, John Morton, Warren Ladiges","publishingOrg":null,"publicationYear":2020,"doi":"10.31491/apt.2020.03.014","pubmedId":"35083444","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning The potential of GHK as an anti-aging peptide.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.31491/apt.2020.03.014","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article"]},"provenancePayload":{"doi":"10.31491/apt.2020.03.014","pmid":"35083444","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"a981414859b54271e8053abfac20e2be","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Evaluation of the effects of topical tripeptide-copper complex and zinc oxide on open-wound healing in rabbits","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/?term=%22Evaluation%20of%20the%20effects%20of%20topical%20tripeptide-copper%20complex%22","evidenceTier":"animal","summary":"A controlled rabbit model evaluated topical tripeptide-copper complex and reported wound-healing effects in an animal setting.","authors":null,"publishingOrg":null,"publicationYear":2006,"doi":null,"pubmedId":null,"jurisdiction":null,"dateAccessed":"2026-09-08T18:31:47.338Z","editorialNotes":"AI-assisted synthesis; 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Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Paulina Marta Gajda; Niels Bjerre Holm; Lars Jakobsen Hoej; Brian Schou Rasmussen; Petur Weihe Dalsgaard; Lotte Ask Reitzel; Kristian Linnet","publishingOrg":"Drug testing and analysis","publicationYear":2019,"doi":"10.1002/dta.2489","pubmedId":"30136411","jurisdiction":null,"dateAccessed":"2026-09-09T11:42:47.093Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1002/dta.2489","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:42:47.093Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"mechanistic","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article"},"provenancePayload":{"doi":"10.1002/dta.2489","pmid":"30136411","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:42:47.093Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"6d89aab6-caec-5790-9e7a-b0ffcae46058","peptideId":"85f9bc7c-6257-44b5-b7b0-3f7f194ee1cd","title":"Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/27548147/","evidenceTier":"laboratory","summary":"PubMed-indexed journal article examining growth hormone releasing peptide-2 attenuation of protein kinase c-induced inflammation in human ovarian granulosa cells. Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Yi-Ning Chao; David Sun; Yen-Chun Peng; Yuh-Lin Wu","publishingOrg":"International journal of molecular sciences","publicationYear":2016,"doi":"10.1074/jbc.270.42.24965","pubmedId":"27548147","jurisdiction":null,"dateAccessed":"2026-09-09T11:42:47.093Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1074/jbc.270.42.24965","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:42:47.093Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"in_vitro","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article"},"provenancePayload":{"doi":"10.1074/jbc.270.42.24965","pmid":"27548147","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:42:47.093Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"6c2397a6-2f0b-5096-907e-573f2ecf0028","peptideId":"85f9bc7c-6257-44b5-b7b0-3f7f194ee1cd","title":"Analysis of new growth promoting black market products.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/29864719/","evidenceTier":"observational","summary":"PubMed-indexed journal article; research support, non-u.s. gov't examining analysis of new growth promoting black market products. Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Oliver Krug; Andreas Thomas; Helle Malerød-Fjeld; Yvette Dehnes; Tim Laussmann; Ingo Feldmann; Albert Sickmann; Mario Thevis","publishingOrg":"Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society","publicationYear":2018,"doi":"10.1016/j.ghir.2018.05.001","pubmedId":"29864719","jurisdiction":null,"dateAccessed":"2026-09-09T11:42:47.093Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/j.ghir.2018.05.001","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:42:47.093Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"mechanistic","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article; Research Support, Non-U.S. Gov't"},"provenancePayload":{"doi":"10.1016/j.ghir.2018.05.001","pmid":"29864719","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:42:47.093Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"19bdc25a-9c08-500e-9c34-9c1e5a8b5b8e","peptideId":"85f9bc7c-6257-44b5-b7b0-3f7f194ee1cd","title":"ACTH releasing activity of KP-102 (GHRP-2) in rats is mediated mainly by release of CRF.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/15645295/","evidenceTier":"animal","summary":"PubMed-indexed journal article examining acth releasing activity of kp-102 (ghrp-2) in rats is mediated mainly by release of crf. Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Chiharu Hirotani; Yutaka Oki; Kiyoharu Ukai; Tadashi Okuno; Shigeru Kurasaki; Tadashi Ohyama; Naomi Doi; Ken Sasaki; Katsuhiko Ase","publishingOrg":"Naunyn-Schmiedeberg's archives of pharmacology","publicationYear":2005,"doi":"10.1007/s00210-004-1009-3","pubmedId":"15645295","jurisdiction":null,"dateAccessed":"2026-09-09T11:42:47.093Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1007/s00210-004-1009-3","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:42:47.093Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"animal_in_vivo","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article"},"provenancePayload":{"doi":"10.1007/s00210-004-1009-3","pmid":"15645295","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:42:47.093Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"84f7aaac-ea48-5b8d-b3a5-fce2e4d43e10","peptideId":"85f9bc7c-6257-44b5-b7b0-3f7f194ee1cd","title":"Evaluation of growth hormone-releasing peptide-2 for diagnosis of thyrotropin-producing pituitary adenomas.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/29973439/","evidenceTier":"observational","summary":"PubMed-indexed journal article examining evaluation of growth hormone-releasing peptide-2 for diagnosis of thyrotropin-producing pituitary adenomas. Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Kazunori Kageyama; Satoru Sakihara; Wataru Kameda; Aya Sugiyama; Shinobu Takayasu; Ken Terui; Makoto Daimon","publishingOrg":"Endocrine journal","publicationYear":2018,"doi":"10.1507/endocrj.EJ17-0527","pubmedId":"29973439","jurisdiction":null,"dateAccessed":"2026-09-09T11:42:47.093Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1507/endocrj.ej17-0527","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:42:47.093Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"mechanistic","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article"},"provenancePayload":{"doi":"10.1507/endocrj.EJ17-0527","pmid":"29973439","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:42:47.093Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"4da1ddc6-3708-5317-bc7b-ff4269edf9d7","peptideId":"85f9bc7c-6257-44b5-b7b0-3f7f194ee1cd","title":"Detection of black market follistatin 344.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/31758732/","evidenceTier":"observational","summary":"PubMed-indexed journal article examining detection of black market follistatin 344. Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Christian Reichel; Günter Gmeiner; Mario Thevis","publishingOrg":"Drug testing and analysis","publicationYear":2019,"doi":"10.1002/dta.2741","pubmedId":"31758732","jurisdiction":null,"dateAccessed":"2026-09-09T11:42:47.093Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1002/dta.2741","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:42:47.093Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"mechanistic","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article"},"provenancePayload":{"doi":"10.1002/dta.2741","pmid":"31758732","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:42:47.093Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"9d56a3a2-0811-587c-9941-b873317bb984","peptideId":"85f9bc7c-6257-44b5-b7b0-3f7f194ee1cd","title":"Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/15699539/","evidenceTier":"observational","summary":"PubMed-indexed journal article; research support, u.s. gov't, p.h.s. examining growth hormone releasing peptide-2 (ghrp-2), like ghrelin, increases food intake in healthy men. Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Blandine Laferrère; Cynthia Abraham; Colleen D Russell; Cyril Y Bowers","publishingOrg":"The Journal of clinical endocrinology and metabolism","publicationYear":2005,"doi":"10.1210/jc.2004-1719","pubmedId":"15699539","jurisdiction":null,"dateAccessed":"2026-09-09T11:42:47.093Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1210/jc.2004-1719","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:42:47.093Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"mechanistic","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article; Research Support, U.S. Gov't, P.H.S."},"provenancePayload":{"doi":"10.1210/jc.2004-1719","pmid":"15699539","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:42:47.093Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"f875a7bf-fc7f-5539-9220-b742e7405a5d","peptideId":"85f9bc7c-6257-44b5-b7b0-3f7f194ee1cd","title":"Intraportal infusion of ghrelin could inhibit glucose-stimulated GLP-1 secretion by enteric neural net in Wistar rat.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/25247193/","evidenceTier":"observational","summary":"PubMed-indexed journal article; research support, non-u.s. gov't examining intraportal infusion of ghrelin could inhibit glucose-stimulated glp-1 secretion by enteric neural net in wistar rat. 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Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"B S Shepherd; S M Eckert; I S Parhar; M M Vijayan; I Wakabayashi; T Hirano; E G Grau; T T Chen","publishingOrg":"The Journal of endocrinology","publicationYear":2000,"doi":"10.1677/joe.0.167r007","pubmedId":"11115782","jurisdiction":null,"dateAccessed":"2026-09-09T11:42:47.093Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1677/joe.0.167r007","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:42:47.093Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"mechanistic","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S."},"provenancePayload":{"doi":"10.1677/joe.0.167r007","pmid":"11115782","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:42:47.093Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"ab58134e-0dd5-50db-8d91-0b55c7b076cf","peptideId":"85f9bc7c-6257-44b5-b7b0-3f7f194ee1cd","title":"KP-102 (growth hormone-releasing peptide-2) attenuates ischemia/reperfusion injury in isolated rat hearts.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/16773386/","evidenceTier":"animal","summary":"PubMed-indexed journal article examining kp-102 (growth hormone-releasing peptide-2) attenuates ischemia/reperfusion injury in isolated rat hearts. 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Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"John T Sigalos; Alexander W Pastuszak; Andrew Allison; Samuel J Ohlander; Amin Herati; Mark C Lindgren; Larry I Lipshultz","publishingOrg":"American journal of men's health","publicationYear":2017,"doi":"10.1385/endo:22:1:25","pubmedId":"28830317","jurisdiction":null,"dateAccessed":"2026-09-09T11:42:47.093Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1385/endo:22:1:25","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:42:47.093Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"mechanistic","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article"},"provenancePayload":{"doi":"10.1385/endo:22:1:25","pmid":"28830317","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:42:47.093Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"cc02c9e1-3709-5711-bfc2-9a2ec86d84ae","peptideId":"85f9bc7c-6257-44b5-b7b0-3f7f194ee1cd","title":"Association between overweight and growth hormone secretion in patients with non-functioning pituitary tumors.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/35452483/","evidenceTier":"observational","summary":"PubMed-indexed journal article; research support, non-u.s. gov't examining association between overweight and growth hormone secretion in patients with non-functioning pituitary tumors. 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Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Kazuo Chihara; Akira Shimatsu; Naomi Hizuka; Toshiaki Tanaka; Yoshiki Seino; Yuzuru Katofor; KP-102 Study Group","publishingOrg":"European journal of endocrinology","publicationYear":2007,"doi":"10.1530/EJE-07-0066","pubmedId":"17609397","jurisdiction":null,"dateAccessed":"2026-09-09T11:42:47.093Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1530/eje-07-0066","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:42:47.093Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"human_interventional","extractionPayload":{"sourceStrength":{"grade":"B","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't; Validation Study"},"provenancePayload":{"doi":"10.1530/EJE-07-0066","pmid":"17609397","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:42:47.093Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"e75052d8-5b9f-5695-a400-67aa84f9c184","peptideId":"85f9bc7c-6257-44b5-b7b0-3f7f194ee1cd","title":"Structure-activity relationship for peptídic growth hormone secretagogues.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/26811125/","evidenceTier":"observational","summary":"PubMed-indexed journal article examining structure-activity relationship for peptídic growth hormone secretagogues. 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Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Xiaoyu Hu; Beihua Xu; Ziniu Zhou","publishingOrg":"AAPS PharmSciTech","publicationYear":2015,"doi":"10.1007/s12272-010-0718-z","pubmedId":"25761386","jurisdiction":null,"dateAccessed":"2026-09-09T11:42:47.093Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1007/s12272-010-0718-z","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:42:47.093Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"mechanistic","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article"},"provenancePayload":{"doi":"10.1007/s12272-010-0718-z","pmid":"25761386","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:42:47.093Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"8f1255be-5d22-5065-a16d-1e75bd34d835","peptideId":"85f9bc7c-6257-44b5-b7b0-3f7f194ee1cd","title":"Determination of the immunostimulatory drug-glucosoaminyl-muramyl-dipeptide-in human plasma using HPLC-MS/MS and its application to a pharmacokinetic study.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/32652605/","evidenceTier":"observational","summary":"PubMed-indexed journal article examining determination of the immunostimulatory drug-glucosoaminyl-muramyl-dipeptide-in human plasma using hplc-ms/ms and its application to a pharmacokinetic study. 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Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Arancha Delgado-Rubín de Célix; Julie A Chowen; Jesús Argente; Laura M Frago","publishingOrg":"Journal of neurochemistry","publicationYear":2006,"doi":"10.1111/j.1471-4159.2006.04122.x","pubmedId":"17076656","jurisdiction":null,"dateAccessed":"2026-09-09T11:43:01.757Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1111/j.1471-4159.2006.04122.x","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:43:01.757Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"mechanistic","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article; Research Support, Non-U.S. Gov't"},"provenancePayload":{"doi":"10.1111/j.1471-4159.2006.04122.x","pmid":"17076656","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:43:01.757Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"1ed68521-13c3-5165-8b8f-8006dd697800","peptideId":"6657d302-0ceb-42c8-9ba6-bc6b358b8e0c","title":"Growth hormone (GH)-releasing peptide-6 requires endogenous hypothalamic GH-releasing hormone for maximal GH stimulation.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/9543138/","evidenceTier":"phase_1_2","summary":"PubMed-indexed clinical trial; journal article; randomized controlled trial; research support, u.s. gov't, non-p.h.s.; research support, u.s. gov't, p.h.s. examining growth hormone (gh)-releasing peptide-6 requires endogenous hypothalamic gh-releasing hormone for maximal gh stimulation. 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Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"W Locke; H D Kirgis; C Y Bowers; A A Abdoh","publishingOrg":"Life sciences","publicationYear":1995,"doi":"10.1016/0024-3205(95)00087-9","pubmedId":"8614257","jurisdiction":null,"dateAccessed":"2026-09-09T11:43:01.757Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/0024-3205(95)00087-9","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:43:01.757Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"animal_in_vivo","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article"},"provenancePayload":{"doi":"10.1016/0024-3205(95)00087-9","pmid":"8614257","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:43:01.757Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"460d7148-fd46-57fe-9835-540b64504c27","peptideId":"6657d302-0ceb-42c8-9ba6-bc6b358b8e0c","title":"Growth hormone releasing peptide-6 (GHRP-6) prevents doxorubicin-induced myocardial and extra-myocardial damages by activating prosurvival mechanisms.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/38873418/","evidenceTier":"observational","summary":"PubMed-indexed journal article examining growth hormone releasing peptide-6 (ghrp-6) prevents doxorubicin-induced myocardial and extra-myocardial damages by activating prosurvival mechanisms. Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Jorge Berlanga-Acosta; Danay Cibrian; Juan Valiente-Mustelier; José Suárez-Alba; Ariana García-Ojalvo; Viviana Falcón-Cama; Baohong Jiang; Linlin Wang; Gerardo Guillén-Nieto","publishingOrg":"Frontiers in pharmacology","publicationYear":2024,"doi":"10.1155/S1110724302000335","pubmedId":"38873418","jurisdiction":null,"dateAccessed":"2026-09-09T11:43:01.757Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1155/s1110724302000335","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:43:01.757Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"mechanistic","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article"},"provenancePayload":{"doi":"10.1155/S1110724302000335","pmid":"38873418","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:43:01.757Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"174ef9c4-1265-53ae-afda-d5253b53635f","peptideId":"6657d302-0ceb-42c8-9ba6-bc6b358b8e0c","title":"Growth hormone-releasing peptide-6 stimulates sleep, growth hormone, ACTH and cortisol release in normal man.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/7617137/","evidenceTier":"phase_1_2","summary":"PubMed-indexed clinical trial; journal article; randomized controlled trial; research support, non-u.s. gov't examining growth hormone-releasing peptide-6 stimulates sleep, growth hormone, acth and cortisol release in normal man. 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Ipamorelin is a synthetic peptide with GH releasing properties. We wished to study the metabolic effects of Ipamorelin and GH on sel …","authors":"Aagaard NK, Grøfte T, Greisen J, Malmlöf K, Johansen PB, Grønbaek H, Ørskov H, Tygstrup N, Vilstrup H.","publishingOrg":null,"publicationYear":2009,"doi":"10.1016/j.ghir.2009.01.001","pubmedId":"19231263","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. 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The pituitary GH content was unchanged by ipamorelin treatme …","authors":"Johansen PB, Nowak J, Skjaerbaek C, Flyvbjerg A, Andreassen TT, Wilken M, Orskov H.","publishingOrg":null,"publicationYear":1999,"doi":"10.1054/ghir.1999.9998","pubmedId":"10373343","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. Relationship to named compound is explicitly classified.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats.","supportNature":"contextualizes","qualification":"Compound-specific evidence is preclinical, mechanistic, or otherwise insufficient to establish human clinical efficacy or safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-eight-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1054/ghir.1999.9998","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T19:33:45.384Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ipamorelin:wave2:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Compound-specific evidence is preclinical, mechanistic, or otherwise insufficient to establish human clinical efficacy or safety."],"studyDesign":"Animal in-vivo study","sourceStrength":{"note":"Automated structured-metadata baseline; full-text risk-of-bias review may revise this rating.","grade":"C","score":60,"version":"WPF-ESR-1.0","dimensions":{"authority":78,"reporting":68,"directness":88,"replication":45,"designAndBias":46,"populationRelevance":25},"provisional":true},"directCompoundEvidence":true,"relationshipToNamedCompound":"direct_compound"},"provenancePayload":{"doi":"10.1054/ghir.1999.9998","pmid":"10373343","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"relationshipClassified":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T19:33:45.384Z","updatedAt":"2026-09-08T19:33:45.384Z"},{"id":"7ab19f3a1e88e6fc26521c77c190c301","peptideId":"784642c5-02af-431f-9f06-a200532f0d31","title":"Therapeutic peptides in gerontology: mechanisms and applications for healthy aging.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/42021992/","evidenceTier":"phase_1_2","summary":"Search terms included \"peptide therapeutics,\" \"aging,\" \"gerontology,\" \"healthspan,\" combined with specific peptide names (tirzepatide, epitalon, GHK-Cu, BPC-157, TB-500, Semax, CJC-1295, ipamorelin, bremelanotide). Peer-reviewed articles, clinical trials, regulatory docume …","authors":"Mavrych V, Shypilova I, Bolgova O.","publishingOrg":null,"publicationYear":2026,"doi":"10.3389/fragi.2026.1790247","pubmedId":"42021992","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. 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The structure of these peptides was characterised by means of high resolution (tandem) mass sp …","authors":"Krug O, Thomas A, Malerød-Fjeld H, Dehnes Y, Laussmann T, Feldmann I, Sickmann A, Thevis M.","publishingOrg":null,"publicationYear":2018,"doi":"10.1016/j.ghir.2018.05.001","pubmedId":"29864719","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. 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The potential of anamorelin to inhibit electrical field …","authors":"Lu Z, Ngan MP, Liu JYH, Yang L, Tu L, Chan SW, Giuliano C, Lovati E, Pietra C, Rudd JA.","publishingOrg":null,"publicationYear":2024,"doi":"10.1016/j.physbeh.2024.114644","pubmedId":"39043357","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. 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All are potent GH and IGF-1 stimulators that can significantly improve body composition while ameliorating specific hypogonadal symptoms inclu …","authors":"Sinha DK, Balasubramanian A, Tatem AJ, Rivera-Mirabal J, Yu J, Kovac J, Pastuszak AW, Lipshultz LI.","publishingOrg":null,"publicationYear":2020,"doi":"10.21037/tau.2019.11.30","pubmedId":"32257855","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. 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Ipamorelin is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2), which displays high GH releasing potency and efficacy in vitro and in vivo. ...The specificity …","authors":"Raun K, Hansen BS, Johansen NL, Thøgersen H, Madsen K, Ankersen M, Andersen PH.","publishingOrg":null,"publicationYear":1998,"doi":"10.1530/eje.0.1390552","pubmedId":"9849822","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. 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RESULTS: BPC-157 demonstrated potential benefits in tendon and muscle repair, but these findings are largely unvalidated in human trials. ...TB-4 and its derivative TB-50 …","authors":"Mayfield CK, Bolia IK, Feingold CL, Lin EH, Liu JN, Rick Hatch GF, Gamradt SC, Weber AE.","publishingOrg":null,"publicationYear":2026,"doi":"10.1177/03635465251357593","pubmedId":"41476424","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. 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Use of peptide and peptide-analog drugs in recreational and professional sport and bodybuilding: a critical review.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/41880199/","evidenceTier":"laboratory","summary":"Marketed as more selective and ostensibly safer alternatives, peptides-including growth hormone secretagogues (e.g., Ipamorelin), growth hormone-releasing hormone analogues (e.g., CJC-1295, Sermorelin), and synthetic fragments (e.g., Frag 176-191, KPV)-are promoted for mus …","authors":"Coutinho LFD, DE Oliveira Neves LF, Camilo RP.","publishingOrg":null,"publicationYear":2026,"doi":"10.23736/S0022-4707.26.17773-1","pubmedId":"41880199","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. Relationship to named compound is explicitly classified.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes mechanistic evidence concerning A new era of doping? 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Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Ahmet Hakan Gedik; Erkan Cakir; Yasemin Gokdemir; Zeynep Seda Uyan; Abdurrahim Kocyigit; Emel Torun; Bulent Karadag; Refika Ersu; Fazilet Karakoc","publishingOrg":"The clinical respiratory journal","publicationYear":2017,"doi":"10.1111/crj.12331","pubmedId":"26073571","jurisdiction":null,"dateAccessed":"2026-09-09T11:43:32.996Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1111/crj.12331","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:43:32.996Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"mechanistic","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article; Multicenter Study"},"provenancePayload":{"doi":"10.1111/crj.12331","pmid":"26073571","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:43:32.996Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"df275285-8d01-5f33-ba61-e654942e4668","peptideId":"e56dabb2-2ca7-45f8-994b-42c556d87ce1","title":"Human cathelicidin, LL-37, inhibits respiratory syncytial virus infection in polarized airway epithelial cells.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/26732674/","evidenceTier":"laboratory","summary":"PubMed-indexed journal article examining human cathelicidin, ll-37, inhibits respiratory syncytial virus infection in polarized airway epithelial cells. Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Jennifer L Harcourt; Melissa McDonald; Pavel Svoboda; Jan Pohl; Kathleen Tatti; Lia M Haynes","publishingOrg":"BMC research notes","publicationYear":2016,"doi":"10.1084/jem.188.10.1967","pubmedId":"26732674","jurisdiction":null,"dateAccessed":"2026-09-09T11:43:32.996Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1084/jem.188.10.1967","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:43:32.996Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"in_vitro","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article"},"provenancePayload":{"doi":"10.1084/jem.188.10.1967","pmid":"26732674","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:43:32.996Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"b6eada27-21f5-5d76-90eb-c0dc43be7eff","peptideId":"e56dabb2-2ca7-45f8-994b-42c556d87ce1","title":"The impact of cathelicidin, the human antimicrobial peptide LL-37 in urinary tract infections.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/29310594/","evidenceTier":"observational","summary":"PubMed-indexed journal article examining the impact of cathelicidin, the human antimicrobial peptide ll-37 in urinary tract infections. Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Ibrahim H Babikir; Elsir A Abugroun; Naser Eldin Bilal; Abdullah Ali Alghasham; Elmuataz Elmansi Abdalla; Ishag Adam","publishingOrg":"BMC infectious diseases","publicationYear":2018,"doi":"10.1126/science.282.5393.1494","pubmedId":"29310594","jurisdiction":null,"dateAccessed":"2026-09-09T11:43:32.996Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1126/science.282.5393.1494","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:43:32.996Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"mechanistic","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article"},"provenancePayload":{"doi":"10.1126/science.282.5393.1494","pmid":"29310594","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:43:32.996Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"171362e8-9790-57ea-9c46-63f74805afce","peptideId":"e56dabb2-2ca7-45f8-994b-42c556d87ce1","title":"Cathelicidin LL-37 peptide regulates endothelial cell stiffness and endothelial barrier permeability.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/20943960/","evidenceTier":"laboratory","summary":"PubMed-indexed journal article; research support, n.i.h., extramural; research support, non-u.s. gov't examining cathelicidin ll-37 peptide regulates endothelial cell stiffness and endothelial barrier permeability. Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Fitzroy J Byfield; Qi Wen; Katarzyna Leszczynska; Alina Kulakowska; Zbigniew Namiot; Paul A Janmey; Robert Bucki","publishingOrg":"American journal of physiology. 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Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Lamia Hamouda Elgarhy; Basma Ramadan Refaey Ramadan; Fersan Abd Allah Sallam; Dalya Ayman Iskandarani; El-Sayed Shaaban Hewedy","publishingOrg":"Archives of dermatological research","publicationYear":2025,"doi":"10.1080/09546634.2020.1757018","pubmedId":"39873762","jurisdiction":null,"dateAccessed":"2026-09-09T11:43:32.996Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1080/09546634.2020.1757018","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:43:32.996Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"mechanistic","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article"},"provenancePayload":{"doi":"10.1080/09546634.2020.1757018","pmid":"39873762","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:43:32.996Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"0445ae40-1ac1-5d90-b71e-327ae9cd9dc3","peptideId":"e56dabb2-2ca7-45f8-994b-42c556d87ce1","title":"Human cathelicidin LL-37 inhibits platelet aggregation and thrombosis via Src/PI3K/Akt signaling.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/27012197/","evidenceTier":"observational","summary":"PubMed-indexed journal article; research support, non-u.s. gov't examining human cathelicidin ll-37 inhibits platelet aggregation and thrombosis via src/pi3k/akt signaling. Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Wen Su; Yahui Chen; Caihui Wang; Xue Ding; Gamariel Rwibasira; Yi Kong","publishingOrg":"Biochemical and biophysical research communications","publicationYear":2016,"doi":"10.1016/j.bbrc.2016.03.095","pubmedId":"27012197","jurisdiction":null,"dateAccessed":"2026-09-09T11:43:32.996Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/j.bbrc.2016.03.095","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:43:32.996Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"mechanistic","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article; Research Support, Non-U.S. Gov't"},"provenancePayload":{"doi":"10.1016/j.bbrc.2016.03.095","pmid":"27012197","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:43:32.996Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"2b53e8b4-b293-5da9-99de-720296dbf81f","peptideId":"e56dabb2-2ca7-45f8-994b-42c556d87ce1","title":"Cathelicidin LL-37 Activates Human Keratinocyte Autophagy through the P2X₇, Mechanistic Target of Rapamycin, and MAPK Pathways.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/36455652/","evidenceTier":"observational","summary":"PubMed-indexed journal article; research support, non-u.s. gov't examining cathelicidin ll-37 activates human keratinocyte autophagy through the p2x₇, mechanistic target of rapamycin, and mapk pathways. 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Initial continuous exposure can transiently increase luteinizing hormone, follicle-stimulating hormone, and gonadal steroid concentrations; sustained depot exposure then desensitizes pituitary GnRH signaling and suppresses gonadal steroid production. This biphasic action supports product-specific uses in prostate cancer, central precocious puberty, endometriosis, and uterine fibroids, while stimulation-test and assisted-reproduction contexts use different timing and objectives.","evidenceQualitySummary":"The governed 25-source corpus spans foundational pharmacokinetics, prostate-cancer androgen deprivation and comparative antagonist trials, cardiovascular outcomes, central-precocious-puberty monitoring and formulation studies, endometriosis and add-back therapy, uterine-fibroid and perioperative trials, assisted reproduction, large prospective practice data, and systematic reviews. PubMed titles, authorship, DOI/PMID, publication metadata, molecule relevance, active source status, and duplication were verified. Comparator trials are labeled as such and do not turn evidence about another drug into evidence for unstudied leuprolide effects.","safetyConcernsSummary":"The initial hormonal flare can temporarily worsen disease manifestations in susceptible patients. Longer suppression can affect bone density, vasomotor symptoms, mood, sexual function, fertility, body composition, glucose and cardiovascular risk; pediatric monitoring and pregnancy exclusions require indication-specific attention. Depot products and intervals are not automatically interchangeable. Trial eras, open-label designs, surrogate endpoints, background therapies, and sponsor involvement limit some comparisons. 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Humanin and its homologs and MOTS-c are two of several MDPs hypothesized to have …","authors":"Mendelsohn AR, Larrick JW.","publishingOrg":null,"publicationYear":2018,"doi":"10.1089/rej.2018.2114","pubmedId":"30058454","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. 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CONCLUSION: M …","authors":"Lin C, Luo L, Xun Z, Zhu C, Huang Y, Ye Y, Zhang J, Chen T, Wu S, Zhan F, Yang B, Liu C, Ran N, Ou Q.","publishingOrg":null,"publicationYear":2024,"doi":"10.1136/gutjnl-2023-330389","pubmedId":"37788894","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. 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CONCLUSIONS: The circulating MOTS-c is associated with an increased r …","authors":"Cao P, Wang B, Zhang N, Yang J, Tong Q, Gong Z.","publishingOrg":null,"publicationYear":2025,"doi":"10.1161/JAHA.125.041905","pubmedId":"41368821","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. 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In ongoing trials investigators are interrogating the efficacy of these agents for new indications, including metabolic liver disease, peripheral artery disease, Parkinson disease, and Alzheimer disease. The success of GLP-1-based medicines has spurred the development of new molecular entities and combinations with unique pharmacokinetic and pharmacodynamic profiles, exemplified by tirzepatide, a GIP-GLP-1 receptor coagonist. 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Retatrutide, an innovative agent, represents a potential advancement in therapy; however, its performance and safety profile specifically in a CKD population are not fully determined yet. This meta-analysis and systematic review sought to consolidate existing research on the use of retatrutide in this comorbid patient group. A comprehensive literature search identified relevant randomized controlled trials for inclusion. Reductions in glycated hemoglobin (HbA1c) and body weight were the primary goals for evaluating effectiveness,...","authors":"Kumari Pallavi, Anshuman Chandra, Keshav Kumar, Kumar Martand, Shyam Sundar Sahu, Lalit Mohan, Anita Verma","publishingOrg":null,"publicationYear":2025,"doi":"10.26574/maedica.2025.20.4.824","pubmedId":"41537067","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Efficacy and Safety of Retatrutide in the Treatment of Diabetes and/or Obesity Comorbid with Chronic Kidney disease: a Systematic Review and Meta-Analysis.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.26574/maedica.2025.20.4.824","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:retatrutide:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Narrative or scoped review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.26574/maedica.2025.20.4.824","pmid":"41537067","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"b5b1b5da9e19913043e61dafdd4905d7","peptideId":"19f90754-bf7b-4457-8118-15f84ee97aae","title":"The Triple-Agonist Revolution: Retatrutide and the Paradigm Shift in Multi-Hormonal Pharmacotherapy for Obesity and Cardiometabolic Comorbidities.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/41545327/","evidenceTier":"insufficient","summary":"Obesity has emerged as a global health crisis requiring innovative therapeutic strategies beyond conventional approaches. While glucagon-like peptide-1 (GLP-1) and dual GIP/GLP-1 receptor agonists have redefined pharmacological management, their limitations necessitate further innovation. Retatrutide (LY3437943), a novel triple agonist targeting GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors, represents a transformative advance in obesity pharmacotherapy. Phase 2 trials report unprecedented weight reductions, comparable to bariatric surgery, with additional benefits for metabolic comorbidities such as NASH and cardiovascular disease. Retatrutide...","authors":"Nila Ganamurali, Sarvesh Sabarathinam","publishingOrg":null,"publicationYear":2026,"doi":"10.1002/cpdd.70001","pubmedId":"41545327","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning The Triple-Agonist Revolution: Retatrutide and the Paradigm Shift in Multi-Hormonal Pharmacotherapy for Obesity and Cardiometabolic Comorbidities.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1002/cpdd.70001","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:retatrutide:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Narrative or scoped review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.1002/cpdd.70001","pmid":"41545327","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"77c668ca92bfea1284f641251bfcf5ce","peptideId":"19f90754-bf7b-4457-8118-15f84ee97aae","title":"Appetite, eating attitudes, and eating behaviours during treatment with retatrutide in adults with type 2 diabetes: Results of a phase 2 study.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/40916752/","evidenceTier":"phase_1_2","summary":"To determine whether adults with type 2 diabetes (T2D) treated with retatrutide report greater changes in self-reported appetite, dietary restraint, and disinhibition compared to placebo or dulaglutide and to examine associations with weight change. These pre-specified exploratory analyses examined changes from baseline in Appetite Visual Analogue Scale (VAS) and Eating Inventory (EI) scores after 24 and 36 weeks of once-weekly treatment with placebo, dulaglutide 1.5 mg, or retatrutide 0.5, 4, 8, or 12 mg in 275 adults with T2D. Changes from baseline with retatrutide were compared to those with placebo and dulaglutide. Post-hoc correlations between changes in body weight and Appetite...","authors":"Chisom Kanu, Kristina S Boye, Jiat Ling Poon, Iris Goetz, Suzanne Williamson, Jitong Lou, Mark L Hartman, Corby K Martin","publishingOrg":null,"publicationYear":2025,"doi":"10.1111/dom.70097","pubmedId":"40916752","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Appetite, eating attitudes, and eating behaviours during treatment with retatrutide in adults with type 2 diabetes: Results of a phase 2 study.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1111/dom.70097","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:retatrutide:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":86,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Clinical Trial, Phase II","Randomized Controlled Trial"]},"provenancePayload":{"doi":"10.1111/dom.70097","pmid":"40916752","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"9e5d38fdf25d7ccd2c131a69b9119337","peptideId":"19f90754-bf7b-4457-8118-15f84ee97aae","title":"Decreases in circulating ANGPTL3/8 concentrations following retatrutide treatment parallel reductions in serum lipids.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/40726454/","evidenceTier":"phase_1_2","summary":"The aim of this study was to determine if retatrutide, a triple agonist of glucose-dependent insulinotropic polypeptide (GIP) receptor, glucagon-like peptide 1 (GLP-1) receptor and glucagon (GCG) receptor, may lower serum triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels in part by decreasing circulating concentrations of the angiopoietin-like protein 3/8 complex (ANGPTL3/8). In post-hoc analyses of two phase 2 retatrutide trials, concentrations of ANGPTL3/8, ANGPTL4/8 complex (ANGPTL4/8), ANGPTL3 and ANGPTL4 were measured using dedicated immunoassays to determine percent changes from baseline. Correlations of ANGPTL protein and complex levels with lipid and...","authors":"Yi Wen, Deven Lemen, Yanzhu Lin, Yan Q Chen, Ajit Regmi, William C Roell, Melissa K Thomas, Mark L Hartman","publishingOrg":null,"publicationYear":2025,"doi":"10.1111/dom.16661","pubmedId":"40726454","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Decreases in circulating ANGPTL3/8 concentrations following retatrutide treatment parallel reductions in serum lipids.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1111/dom.16661","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:retatrutide:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":86,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Clinical Trial, Phase II","Journal Article"]},"provenancePayload":{"doi":"10.1111/dom.16661","pmid":"40726454","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"cbc65747e0366a349075373e73601d4a","peptideId":"19f90754-bf7b-4457-8118-15f84ee97aae","title":"A review of an investigational drug retatrutide, a novel triple agonist agent for the treatment of obesity.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/38367045/","evidenceTier":"insufficient","summary":"Obesity is one of the critical public health problems in our society. It leads to various health conditions, such as type 2 diabetes mellitus, cardiovascular disease, hypertension, dyslipidaemia, and non-alcoholic fatty liver disease. With the rising incidence of obesity, there is a growing demand for new therapies which can effectively manage body weight and improve health. Currently under development, multi-receptor agonist drugs may offer a promising solution to meet this unmet medical need. Retatrutide is a novel triple receptor agonist peptide that targets the glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon-like peptide-1 receptor...","authors":"Manmeet Kaur, Saurav Misra","publishingOrg":null,"publicationYear":2024,"doi":"10.1007/s00228-024-03646-0","pubmedId":"38367045","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning A review of an investigational drug retatrutide, a novel triple agonist agent for the treatment of obesity.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1007/s00228-024-03646-0","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:retatrutide:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Narrative or scoped review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.1007/s00228-024-03646-0","pmid":"38367045","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"dc84663398c71cb112352d6a96599beb","peptideId":"19f90754-bf7b-4457-8118-15f84ee97aae","title":"Retatrutide in type 2 diabetes mellitus and obesity: an overview.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/41785010/","evidenceTier":"insufficient","summary":"Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for T2DM and obesity. An electronic search was conducted in Scopus, PubMed/MEDLINE, and Google Scholar databases. Retatrutide (LY3437943) is a novel triple agonist targeting glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon-like peptide-1 receptor (GLP-1 R). In subjects with type 2 diabetes mellitus (T2DM), decreased glycated hemoglobin (HbA1c) by up to 2.16% and decreased fasting glucose by up to 69.1 mg/dL have been seen. Weight loss up to 16.94% was observed in subjects with T2DM. Subjects with overweight or obesity experienced a greater weight loss by up to...","authors":"Theodoros Panou, Evanthia Gouveri, Djordje S Popovic, Nikolaos Papanas","publishingOrg":null,"publicationYear":2026,"doi":"10.1080/17512433.2026.2642415","pubmedId":"41785010","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Retatrutide in type 2 diabetes mellitus and obesity: an overview.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1080/17512433.2026.2642415","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:retatrutide:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Narrative or scoped review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.1080/17512433.2026.2642415","pmid":"41785010","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"580747886e17110272c71dcdfab5c859","peptideId":"19f90754-bf7b-4457-8118-15f84ee97aae","title":"Efficacy and safety of triple hormone receptor agonist retatrutide for the management of obesity: a systematic review and meta-analysis.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/39817343/","evidenceTier":"observational","summary":"Retatrutide is a novel triple hormone receptor agonist which has shown great promise in tackling obesity in preliminary trials. We did this systematic review and meta-analysis to pool the results of all available trials and ascertain its safety and efficacy in the treatment of obesity. A literature search was conducted in PubMed, Cochrane Central and Embase using appropriate search terms and randomized control trials (RCTs) were identified which reported the safety and efficacy of retatrutide. Data was pooled using mean differences for continuous variables and risk ratios for the safety profile in RStudio. After the initial search four RCTs were included in the analysis which compared...","authors":"Jay Tewari, Khalid Ahmad Qidwai, Ajoy Tewari, Savneet Kaur, Vineeta Tewari, Anuj Maheshwari","publishingOrg":null,"publicationYear":2025,"doi":"10.1080/17512433.2025.2450254","pubmedId":"39817343","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes meta_analysis evidence concerning Efficacy and safety of triple hormone receptor agonist retatrutide for the management of obesity: a systematic review and meta-analysis.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1080/17512433.2025.2450254","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:retatrutide:expansion:2026-09-08","evidenceLane":"meta_analysis","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Systematic review and meta-analysis","sourceStrength":{"grade":"A","score":83,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Meta-Analysis","Systematic Review"]},"provenancePayload":{"doi":"10.1080/17512433.2025.2450254","pmid":"39817343","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"606e78a5d41423f736d42fd0d13995de","peptideId":"19f90754-bf7b-4457-8118-15f84ee97aae","title":"Retatrutide showing promise in obesity (and type 2 diabetes).","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/37947489/","evidenceTier":"insufficient","summary":"Obesity is a major risk factor for cardiovascular disease, diabetes, osteoarthritis, and some cancers. Retatrutide stimulates Glucagon-like peptide 1 (GLP-1), Glucose-dependent insulinotropic polypeptide (GIP) receptors, and glucagon receptors, and is being developed for the treatment of obesity and type 2 diabetes. A phase 2 clinical trial of retatrutide (LY3437943) in the treatment of obesity. The primary end point was percentage change in weight from baseline to 24 weeks, which ranged from -7.2% to -~18% as the dose of retatrutide increased from 1 mg to 12 mg. The most frequent adverse events were gastrointestinal (nausea, diarrhea, vomiting). The results for retatrutide in phase 2...","authors":"Sheila A Doggrell","publishingOrg":null,"publicationYear":2023,"doi":"10.1080/13543784.2023.2283020","pubmedId":"37947489","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Retatrutide showing promise in obesity (and type 2 diabetes).","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1080/13543784.2023.2283020","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:retatrutide:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Narrative or scoped review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.1080/13543784.2023.2283020","pmid":"37947489","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"3974ef681be8cd2fee1336b26ce3001e","peptideId":"19f90754-bf7b-4457-8118-15f84ee97aae","title":"Efficacy of Tirzepatide, Retatrutide, and Semaglutide for Weight Loss in Obese Individuals Without Diabetes.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/40583149/","evidenceTier":"insufficient","summary":"PubMed-indexed narrative or scoped review addressing: Efficacy of Tirzepatide, Retatrutide, and Semaglutide for Weight Loss in Obese Individuals Without Diabetes.","authors":"Bastu Adebayo Olowo-Oribi, Richard James Salway","publishingOrg":null,"publicationYear":2025,"doi":"10.1111/acem.70088","pubmedId":"40583149","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Efficacy of Tirzepatide, Retatrutide, and Semaglutide for Weight Loss in Obese Individuals Without Diabetes.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1111/acem.70088","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:retatrutide:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Narrative or scoped review","sourceStrength":{"grade":"C","score":63,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.1111/acem.70088","pmid":"40583149","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"71b362eac3b5eae01585c7fb83fd3ab8","peptideId":"19f90754-bf7b-4457-8118-15f84ee97aae","title":"Efficacy and safety of retatrutide for the treatment of obesity: a systematic review of clinical trials.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/40728138/","evidenceTier":"observational","summary":"Obesity is a major public health issue linked to various health complications. Retatrutide, a triple agonist peptide targeting the glucagon receptor, GIP receptor, and GLP-1 receptor, shows promise in addressing this need. This systematic review assessed the safety and efficacy of retatrutide for obesity treatment using available clinical trial data. We conducted a comprehensive search of databases, including PubMed, Cochrane and ClinicalTrials.gov, from their inception until March 15, 2025 following PRISMA guidelines. Three articles were included in this systematic review, screening a total of 1,082 patients, with 691 randomly assigned to groups. The average age of participants was...","authors":"Saurav Misra, Ravi Kant Narayan, Manmeet Kaur","publishingOrg":null,"publicationYear":2025,"doi":"10.1515/jbcpp-2025-0113","pubmedId":"40728138","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Efficacy and safety of retatrutide for the treatment of obesity: a systematic review of clinical trials.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1515/jbcpp-2025-0113","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:retatrutide:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Systematic review","sourceStrength":{"grade":"B","score":79,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Systematic Review"]},"provenancePayload":{"doi":"10.1515/jbcpp-2025-0113","pmid":"40728138","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"044665390a1dabff95f8e8b9bbdaaa1d","peptideId":"19f90754-bf7b-4457-8118-15f84ee97aae","title":"The power of three: Retatrutide's role in modern obesity and diabetes therapy.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/39515565/","evidenceTier":"insufficient","summary":"The increasing prevalence of obesity and type 2 diabetes mellitus has resulted in a significant challenge to public health throughout the globe. It required the development of novel therapeutic approaches. Retatrutide is a groundbreaking triple agonist that targets glucagon receptors, gastric inhibitory polypeptide, and glucagon-like peptide-1. Retatrutide's complex mechanism of action involves a synergistic interaction among these receptors, resulting in increased insulin secretion, improved glucose homeostasis, and refined appetite modulation. Clinical trials in phases 1 to 3 have demonstrated significant efficacy, highlighted by significant reductions in body weight and favorable...","authors":"Toufik Abdul-Rahman, Poulami Roy, Fatma Kamal Ahmed, Jann Ludwig Mueller-Gomez, Sarmistha Sarkar, Neil Garg, Victor Oluwafemi Femi-Lawal, Andrew Awuah Wireko","publishingOrg":null,"publicationYear":2024,"doi":"10.1016/j.ejphar.2024.177095","pubmedId":"39515565","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning The power of three: Retatrutide's role in modern obesity and diabetes therapy.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/j.ejphar.2024.177095","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:retatrutide:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Narrative or scoped review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.1016/j.ejphar.2024.177095","pmid":"39515565","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"e49202e342f9783b90980ea411d18680","peptideId":"19f90754-bf7b-4457-8118-15f84ee97aae","title":"Effects of once-weekly subcutaneous retatrutide on weight and metabolic markers: A systematic review and meta-analysis of randomized controlled trials.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/39318607/","evidenceTier":"insufficient","summary":"To assess the effects of once-weekly subcutaneous retatrutide on weight and metabolic markers and the occurrence of side effects in patients with overweight, obesity and/or type 2 diabetes (T2D). PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were systematically searched for placebo-controlled, randomized clinical trials (RCTs) published up until February 23, 2024. Weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) for binary endpoints were computed, with 95 % confidence intervals (CIs). A total of three studies were included, comprising 640 patients, of whom 510 were prescribed retatrutide. Compared with placebo, retatrutide significantly...","authors":"Eric Pasqualotto, Rafael Oliva Morgado Ferreira, Matheus Pedrotti Chavez, Alexandre Hohl, Marcelo Fernando Ronsoni, Tales Pasqualotto, Francisco Cezar Aquino de Moraes, Larissa Hespanhol","publishingOrg":null,"publicationYear":2024,"doi":"10.1016/j.metop.2024.100321","pubmedId":"39318607","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Effects of once-weekly subcutaneous retatrutide on weight and metabolic markers: A systematic review and meta-analysis of randomized controlled trials.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/j.metop.2024.100321","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:retatrutide:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Narrative or scoped review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.1016/j.metop.2024.100321","pmid":"39318607","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"1dff1b908f69f5450bce696643481047","peptideId":"19f90754-bf7b-4457-8118-15f84ee97aae","title":"Efficacy and Safety of GLP-1 Receptor Agonists, Dual Agonists, and Retatrutide for Weight Loss in Adults With Overweight or Obesity: A Bayesian NMA.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/40685589/","evidenceTier":"observational","summary":"To compare the efficacy and safety of GLP-1 receptor agonists (GLP-1RAs), dual agonists (GLP-1RAs/GIP or GCGR), and retatrutide (GLP-1/GIP/glucagon) for weight loss in adults with overweight or obesity. We conducted a systematic review and Bayesian network meta-analysis (NMA) of 19 randomized controlled trials (RCTs) including 29,506 adults (BMI ≥ 25 kg/m2), assessing liraglutide, semaglutide, survodutide, tirzepatide, retatrutide, and placebo. Outcomes included mean weight loss, achievement of ≥ 5%, ≥ 10%, and ≥ 15% weight loss, waist circumference (WC), BMI, and adverse events (AEs) at ≥ 36 weeks. Subgroup and meta-regression analyses evaluated the impact of diabetes status, sex, age,...","authors":"Binayak Sinha, Samit Ghosal","publishingOrg":null,"publicationYear":2025,"doi":"10.1002/oby.24360","pubmedId":"40685589","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Efficacy and Safety of GLP-1 Receptor Agonists, Dual Agonists, and Retatrutide for Weight Loss in Adults With Overweight or Obesity: A Bayesian NMA.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1002/oby.24360","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:retatrutide:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Systematic review","sourceStrength":{"grade":"B","score":79,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Network Meta-Analysis","Systematic Review"]},"provenancePayload":{"doi":"10.1002/oby.24360","pmid":"40685589","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"5709a576bd8ca10733ccae6e8a196981","peptideId":"19f90754-bf7b-4457-8118-15f84ee97aae","title":"Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/42250575/","evidenceTier":"phase_3","summary":"Retatrutide is a GIP, GLP-1, and glucagon triple hormone receptor agonist, under clinical development for type 2 diabetes, obesity, and related complications. We aimed to assess the efficacy and safety of retatrutide as a monotherapy in people with type 2 diabetes that is inadequately controlled by diet and exercise alone. In this 40-week, phase 3, randomised, double-blind, placebo-controlled trial at 48 sites in the USA, Mexico, and India, we recruited adults (aged ≥18 years) with type 2 diabetes that is inadequately controlled by diet and exercise alone, glycated haemoglobin (HbA1c) between 7·0% and 9·5% (53-80 mmol/mol), and BMI of at least 23 kg/m2. Participants were randomly...","authors":"Harpreet S Bajaj, Michelle Welch, Parag Shah, Eduardo Luna, Fatima-Zahra Jaouimaa, Bing Liu, Rong Liu, Yanyun Chen","publishingOrg":null,"publicationYear":2026,"doi":"10.1016/S0140-6736(26)00967-0","pubmedId":"42250575","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/s0140-6736(26)00967-0","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:retatrutide:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":91,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Randomized Controlled Trial","Clinical Trial, Phase III","Multicenter Study"]},"provenancePayload":{"doi":"10.1016/S0140-6736(26)00967-0","pmid":"42250575","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"833dc4cb861e734e5f0bcba2d0016bc5","peptideId":"19f90754-bf7b-4457-8118-15f84ee97aae","title":"Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist for obesity treatment: a systematic review and meta-analysis of randomized controlled trials.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/40291085/","evidenceTier":"insufficient","summary":"Retatrutide is a novel triple agonist targeting the receptors of glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), and glucagon. We sought to assess the efficacy and safety of retatrutide in obese patients with or without diabetes. PubMed, Scopus, Web of Science, and Cochrane databases were searched from inception until May 2024. Eligible studies comprised randomized controlled trials that compared retatrutide with placebo in obese patients. We excluded studies on healthy populations, non-English texts, single-arm studies, animal studies, and abstracts. RevMan software (version 5.4) was used for analysis, with subgroup evaluation by dose (4 mg, 8 mg, 12 mg). Three...","authors":"Alaa Abdrabou Abouelmagd, Amro Mamdouh Abdelrehim, Mohamed Nabih Bashir, Fares Abdelsalam, Ahmed Marey, Yousef Tanas, Duha Milad Abuklish, Mohamed Mohamed Belal","publishingOrg":null,"publicationYear":2025,"doi":"10.1080/08998280.2025.2456441","pubmedId":"40291085","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist for obesity treatment: a systematic review and meta-analysis of randomized controlled trials.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1080/08998280.2025.2456441","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:retatrutide:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Narrative or scoped review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.1080/08998280.2025.2456441","pmid":"40291085","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"e7ce48e424492bfff44eb6f465af378f","peptideId":"19f90754-bf7b-4457-8118-15f84ee97aae","title":"Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/40609566/","evidenceTier":"phase_1_2","summary":"Retatrutide, a glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon receptor agonist, has demonstrated robust glucose and bodyweight reductions in participants with type 2 diabetes. This substudy assessed percent change from baseline to week 36 in total body fat mass versus placebo and dulaglutide. This phase 2, double-blind, parallel-group, placebo-controlled, randomised controlled trial was done in 42 medical centres in the USA. Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m2. Eligible participants were randomly assigned in a 2:2:2:1:1:1:1:2 ratio to once-weekly...","authors":"Tamer Coskun, Qiwei Wu, Nanette C Schloot, Axel Haupt, Zvonko Milicevic, Courtney Khouli, Charles Harris","publishingOrg":null,"publicationYear":2025,"doi":"10.1016/S2213-8587(25)00092-0","pubmedId":"40609566","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/s2213-8587(25)00092-0","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:retatrutide:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":86,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Randomized Controlled Trial","Clinical Trial, Phase II","Multicenter Study"]},"provenancePayload":{"doi":"10.1016/S2213-8587(25)00092-0","pmid":"40609566","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"8d71fb2521055ccecb4170c34c2e8f0f","peptideId":"19f90754-bf7b-4457-8118-15f84ee97aae","title":"Retatrutide-A Game Changer in Obesity Pharmacotherapy.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/40563436/","evidenceTier":"insufficient","summary":"Obesity and type 2 diabetes mellitus (T2DM) are global health crises with significant morbidity and mortality. Retatrutide, a novel triple receptor agonist targeting glucagon-like peptide-1 (GLP-1), Glucose-Dependent Insulinotropic Polypeptide (GIP), and glucagon receptors, represents a groundbreaking advancement in obesity and T2DM pharmacotherapy. This review synthesizes findings from preclinical and clinical studies, highlighting retatrutide's mechanisms, efficacy, and safety profile. Retatrutide's unique molecular structure enables potent activation of GLP-1, GIP, and glucagon receptors, leading to significant weight reduction, improved glycemic control, and favorable metabolic...","authors":"Vasiliki Katsi, Georgios Koutsopoulos, Christos Fragoulis, Kyriakos Dimitriadis, Konstantinos Tsioufis","publishingOrg":null,"publicationYear":2025,"doi":"10.3390/biom15060796","pubmedId":"40563436","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Retatrutide-A Game Changer in Obesity Pharmacotherapy.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.3390/biom15060796","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:retatrutide:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Narrative or scoped review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.3390/biom15060796","pmid":"40563436","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"0895f2a2-32ab-446d-9cf8-94d9bc4cc8c0","peptideId":"19f90754-bf7b-4457-8118-15f84ee97aae","title":"Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/37366315/","evidenceTier":"phase_1_2","summary":"A 48-week phase 2 trial in 338 adults without diabetes found dose-dependent weight reduction; 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In humans, its pharmacologic effects include glucose-dependent stimulation of insulin secretion, reduced glucagon secretion, delayed gastric emptying, reduced calorie intake, and lower body weight. Clinical effects and approved uses depend on the formulation, indication, population, and regulatory jurisdiction; this archive separates those contexts rather than treating semaglutide as a single undifferentiated claim.","evidenceQualitySummary":"Semaglutide now has a governed reference corpus spanning randomized phase 3 weight-management trials, treatment-withdrawal evidence, type 2 diabetes dose and cardiovascular-outcomes programs, cardiovascular outcomes in people without diabetes, chronic kidney disease outcomes, adolescent obesity, oral high-dose obesity treatment, comparative efficacy, systematic synthesis, mechanistic development, and current US regulatory labeling. The corpus distinguishes formulation, dose, population, endpoint, duration, and study design; it also preserves gastrointestinal tolerability, discontinuation, retinopathy, gallbladder, withdrawal-regain, and generalizability qualifications. Evidence is source-level rather than exhaustive: each retained record has a verified DOI/PMID or official FDA identity, a bounded claim, limitations, provenance, and a promotion decision.","safetyConcernsSummary":"Safety is indication- and product-specific. Current U.S. Wegovy labeling carries a boxed warning concerning thyroid C-cell tumors observed in rodents; the relevance to humans is unknown, and the product is contraindicated in people with a personal or family history of medullary thyroid carcinoma or MEN 2. Labelled warnings and precautions include acute pancreatitis, acute gallbladder disease, hypoglycemia with insulin or insulin secretagogues, acute kidney injury due to volume depletion, severe gastrointestinal adverse reactions, hypersensitivity, diabetic-retinopathy complications in people with type 2 diabetes, increased heart rate, and pulmonary aspiration during general anesthesia or deep sedation. This summary is informational, not individualized medical advice; current product labeling and a qualified clinician are the controlling resources.","archiveSummaryNote":"Flagship semaglutide reference profile. Governed sources are selected for decision relevance and program coverage, not to imply that the broader literature contains only the records displayed. Coverage should expand continuously through deduplicated primary studies, systematic reviews, regulatory revisions, trial registrations, safety communications, and post-market evidence.","openQuestionsText":"Key surveillance questions include durability beyond studied periods; outcomes after discontinuation and re-initiation; uncommon and long-latency harms; retinopathy risk modifiers; lean-mass and functional outcomes; effects across underrepresented populations; comparative effectiveness among formulations and incretin therapies; pregnancy and reproductive safety; pediatric long-term outcomes; kidney and heart-failure subgroups; and how real-world adherence modifies trial efficacy.","active":true,"createdAt":"2026-08-18T17:25:06.329Z","updatedAt":"2026-09-09T00:27:05.126Z","entityClass":"peptide_analog","entityClassSource":"human_reviewed","entityClassReviewed":true,"entityClassReviewedBy":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","entityClassReviewedAt":"2026-09-09T00:27:05.126Z","registryStatus":"canonical","registryTier":null,"acquisitionEnabled":true,"publicationState":"published","editorialState":"published","chemistry":{"id":"c03f9816-1736-4e42-996f-b65d9b9037e3","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","molecularFormula":"C187H291N45O59","molecularWeight":4113.58,"aminoAcidSequence":null,"smiles":null,"inchi":null,"inchikey":null,"structureImageUrl":null,"createdAt":"2026-09-08T17:21:53.433Z","updatedAt":"2026-09-08T17:21:53.433Z"},"citations":[{"id":"ae08fcf1395551a3b9401def356a2b41","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/39476339/","evidenceTier":"phase_3","summary":"Weight reduction has been shown to alleviate symptoms of osteoarthritis of the knee, including pain. The effect of glucagon-like peptide-1 receptor agonists on outcomes in knee osteoarthritis among persons with obesity has not been well studied. We conducted a 68-week, double-blind, randomized, placebo-controlled trial at 61 sites in 11 countries. 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Semaglutide produced substantially greater sustained weight reduction; gastrointestinal disorders were the most frequent adverse events.","population":"Adults with overweight or obesity without diabetes","sampleSize":"304","limitations":["The trial population and two-year duration limit broader and longer-term inference; sponsor involvement should be considered."],"studyDesign":"Randomized double-blind placebo-controlled phase 3 trial","sourceStrength":{"note":"Automated baseline based on evidence tier; full-text risk-of-bias review may revise it","grade":"A","score":90,"version":"WPF-ESR-1.0","provisional":true}},"provenancePayload":{"doi":"10.1038/s41591-022-02026-4","pmid":"36216945","reviewBatch":"semaglutide-reference-corpus-2026-09-08"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"48a0dde7-5517-465c-9d06-836483ec4d37","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Semaglutide 2.4 mg once a week in adults from east Asia with overweight or obesity, with or without type 2 diabetes (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/35131037/","evidenceTier":"phase_3","summary":"STEP 6 studied 401 adults in East Asia with overweight or obesity, with or without type 2 diabetes. Semaglutide 2.4 mg produced greater weight reduction than placebo at 68 weeks, with gastrointestinal disorders the most frequent adverse events.","authors":null,"publishingOrg":null,"publicationYear":2022,"doi":"10.1016/S2213-8587(22)00008-0","pubmedId":"35131037","jurisdiction":null,"dateAccessed":"2026-09-08T17:41:50.436Z","editorialNotes":"AI-assisted evidence synthesis; Owner-authorized governed semaglutide corpus expansion on 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-semaglutide-reference-corpus-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/S2213-8587(22)00008-0","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T17:41:50.436Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:semaglutide-reference-corpus:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"finding":"Semaglutide 2.4 mg reduced body weight more than placebo in the studied East Asian population.","summary":"STEP 6 studied 401 adults in East Asia with overweight or obesity, with or without type 2 diabetes. 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At 68 weeks, semaglutide produced greater mean weight reduction than liraglutide; gastrointestinal adverse events were common in both active groups.","authors":null,"publishingOrg":null,"publicationYear":2022,"doi":"10.1001/jama.2021.23619","pubmedId":"35015037","jurisdiction":null,"dateAccessed":"2026-09-08T17:41:50.436Z","editorialNotes":"AI-assisted evidence synthesis; Owner-authorized governed semaglutide corpus expansion on 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-semaglutide-reference-corpus-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1001/jama.2021.23619","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T17:41:50.436Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:semaglutide-reference-corpus:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"finding":"Weekly semaglutide produced greater weight reduction than daily liraglutide over 68 weeks in the studied population.","summary":"STEP 8 randomized 338 adults without diabetes to weekly semaglutide 2.4 mg, daily liraglutide 3.0 mg, or matched placebo. At 68 weeks, semaglutide produced greater mean weight reduction than liraglutide; gastrointestinal adverse events were common in both active groups.","population":"Adults with overweight or obesity without diabetes","sampleSize":"338","limitations":["Active treatments were open-label; dosing schedules differed; the study duration and eligibility criteria limit extrapolation."],"studyDesign":"Randomized open-label active-comparator phase 3b trial with double-blind placebo arms","sourceStrength":{"note":"Automated baseline based on evidence tier; full-text risk-of-bias review may revise it","grade":"A","score":90,"version":"WPF-ESR-1.0","provisional":true}},"provenancePayload":{"doi":"10.1001/jama.2021.23619","pmid":"35015037","reviewBatch":"semaglutide-reference-corpus-2026-09-08"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"109d5f77-28c6-45a2-8531-1f1bad7e35ba","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Once-Weekly Semaglutide in Adolescents with Obesity","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/36322838/","evidenceTier":"phase_3","summary":"In STEP TEENS, 201 adolescents with obesity, or overweight plus a weight-related condition, were randomized to semaglutide 2.4 mg or placebo plus lifestyle intervention for 68 weeks. Semaglutide produced a larger BMI reduction; gastrointestinal events were more frequent and cholelithiasis occurred in the semaglutide group.","authors":null,"publishingOrg":null,"publicationYear":2022,"doi":"10.1056/NEJMoa2208601","pubmedId":"36322838","jurisdiction":null,"dateAccessed":"2026-09-08T17:41:50.436Z","editorialNotes":"AI-assisted evidence synthesis; Owner-authorized governed semaglutide corpus expansion on 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-semaglutide-reference-corpus-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1056/NEJMoa2208601","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T17:41:50.436Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:semaglutide-reference-corpus:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"finding":"Semaglutide plus lifestyle intervention reduced BMI more than placebo plus lifestyle intervention at 68 weeks in enrolled adolescents.","summary":"In STEP TEENS, 201 adolescents with obesity, or overweight plus a weight-related condition, were randomized to semaglutide 2.4 mg or placebo plus lifestyle intervention for 68 weeks. Semaglutide produced a larger BMI reduction; gastrointestinal events were more frequent and cholelithiasis occurred in the semaglutide group.","population":"Adolescents aged 12 to under 18 years with obesity, or overweight plus a weight-related condition","sampleSize":"201","limitations":["Modest sample size, selected adolescent population, 68-week treatment duration, and limited post-treatment follow-up constrain long-term inference."],"studyDesign":"Randomized double-blind placebo-controlled phase 3a trial","sourceStrength":{"note":"Automated baseline based on evidence tier; full-text risk-of-bias review may revise it","grade":"A","score":90,"version":"WPF-ESR-1.0","provisional":true}},"provenancePayload":{"doi":"10.1056/NEJMoa2208601","pmid":"36322838","reviewBatch":"semaglutide-reference-corpus-2026-09-08"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"8b85171b-59b3-48c4-8e7e-c20ffe1e5a8b","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/37952131/","evidenceTier":"phase_3","summary":"SELECT randomized 17,604 adults with established cardiovascular disease and overweight or obesity but no diabetes. Major adverse cardiovascular events occurred in 6.5% with semaglutide and 8.0% with placebo (hazard ratio 0.80); treatment discontinuation for adverse events was more frequent with semaglutide.","authors":null,"publishingOrg":null,"publicationYear":2023,"doi":"10.1056/NEJMoa2307563","pubmedId":"37952131","jurisdiction":null,"dateAccessed":"2026-09-08T17:41:50.436Z","editorialNotes":"AI-assisted evidence synthesis; Owner-authorized governed semaglutide corpus expansion on 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-semaglutide-reference-corpus-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1056/NEJMoa2307563","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T17:41:50.436Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:semaglutide-reference-corpus:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"finding":"Semaglutide 2.4 mg reduced the incidence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke versus placebo during a mean 39.8-month follow-up.","summary":"SELECT randomized 17,604 adults with established cardiovascular disease and overweight or obesity but no diabetes. Major adverse cardiovascular events occurred in 6.5% with semaglutide and 8.0% with placebo (hazard ratio 0.80); treatment discontinuation for adverse events was more frequent with semaglutide.","population":"Adults aged 45 years or older with established cardiovascular disease and BMI at least 27, without diabetes","sampleSize":"17604","limitations":["Applies to secondary-prevention patients with overweight or obesity without diabetes; discontinuation was higher; sponsor involvement and follow-up duration should be considered."],"studyDesign":"Multicenter randomized double-blind placebo-controlled event-driven superiority trial","sourceStrength":{"note":"Automated baseline based on evidence tier; full-text risk-of-bias review may revise it","grade":"A","score":90,"version":"WPF-ESR-1.0","provisional":true}},"provenancePayload":{"doi":"10.1056/NEJMoa2307563","pmid":"37952131","reviewBatch":"semaglutide-reference-corpus-2026-09-08"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"d790dbb0-2827-41f3-9eba-9133f5945b9a","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/31185157/","evidenceTier":"phase_3","summary":"PIONEER 6 randomized 3,183 high-cardiovascular-risk patients with type 2 diabetes to oral semaglutide or placebo. Major adverse cardiovascular events occurred in 3.8% versus 4.8% (hazard ratio 0.79), establishing noninferiority; gastrointestinal events leading to discontinuation were more common with oral semaglutide.","authors":null,"publishingOrg":null,"publicationYear":2019,"doi":"10.1056/NEJMoa1901118","pubmedId":"31185157","jurisdiction":null,"dateAccessed":"2026-09-08T17:41:50.436Z","editorialNotes":"AI-assisted evidence synthesis; Owner-authorized governed semaglutide corpus expansion on 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-semaglutide-reference-corpus-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1056/NEJMoa1901118","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T17:41:50.436Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:semaglutide-reference-corpus:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"finding":"The cardiovascular risk profile of oral semaglutide was noninferior to placebo over a median 15.9 months.","summary":"PIONEER 6 randomized 3,183 high-cardiovascular-risk patients with type 2 diabetes to oral semaglutide or placebo. Major adverse cardiovascular events occurred in 3.8% versus 4.8% (hazard ratio 0.79), establishing noninferiority; gastrointestinal events leading to discontinuation were more common with oral semaglutide.","population":"Patients with type 2 diabetes at high cardiovascular risk","sampleSize":"3183","limitations":["Designed and powered for noninferiority rather than superiority; relatively short median follow-up and high-risk population limit broader inference."],"studyDesign":"Randomized double-blind placebo-controlled event-driven cardiovascular safety trial","sourceStrength":{"note":"Automated baseline based on evidence tier; full-text risk-of-bias review may revise it","grade":"A","score":90,"version":"WPF-ESR-1.0","provisional":true}},"provenancePayload":{"doi":"10.1056/NEJMoa1901118","pmid":"31185157","reviewBatch":"semaglutide-reference-corpus-2026-09-08"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"3763c4d7-1ebf-4bc8-be52-f4e15f4f2200","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Efficacy and safety of once-weekly semaglutide 2.0 mg versus 1.0 mg in patients with type 2 diabetes (SUSTAIN FORTE): a double-blind, randomised, phase 3B trial","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/34293304/","evidenceTier":"phase_3","summary":"SUSTAIN FORTE compared weekly semaglutide 2.0 mg with 1.0 mg in 961 adults with inadequately controlled type 2 diabetes. The 2.0 mg dose achieved modestly greater HbA1c and weight reductions with a broadly similar safety profile.","authors":null,"publishingOrg":null,"publicationYear":2021,"doi":"10.1016/S2213-8587(21)00174-1","pubmedId":"34293304","jurisdiction":null,"dateAccessed":"2026-09-08T17:41:50.436Z","editorialNotes":"AI-assisted evidence synthesis; Owner-authorized governed semaglutide corpus expansion on 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-semaglutide-reference-corpus-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/S2213-8587(21)00174-1","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T17:41:50.436Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:semaglutide-reference-corpus:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"finding":"Semaglutide 2.0 mg provided modest additional glycemic and weight effects versus 1.0 mg in the studied population.","summary":"SUSTAIN FORTE compared weekly semaglutide 2.0 mg with 1.0 mg in 961 adults with inadequately controlled type 2 diabetes. The 2.0 mg dose achieved modestly greater HbA1c and weight reductions with a broadly similar safety profile.","population":"Adults with type 2 diabetes inadequately controlled on metformin with or without sulfonylurea","sampleSize":"961","limitations":["No placebo arm; results apply to the background therapy, baseline control, doses, and 40-week duration studied."],"studyDesign":"Randomized double-blind active-controlled phase 3B trial","sourceStrength":{"note":"Automated baseline based on evidence tier; full-text risk-of-bias review may revise it","grade":"A","score":90,"version":"WPF-ESR-1.0","provisional":true}},"provenancePayload":{"doi":"10.1016/S2213-8587(21)00174-1","pmid":"34293304","reviewBatch":"semaglutide-reference-corpus-2026-09-08"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"af86c3e1-3fa5-48e1-97b2-b5017239c9d5","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/38785209/","evidenceTier":"phase_3","summary":"FLOW randomized 3,533 patients with type 2 diabetes and chronic kidney disease to weekly semaglutide 1.0 mg or placebo. The primary kidney-disease composite risk was lower with semaglutide, and the trial was stopped early after prespecified interim efficacy criteria were met.","authors":null,"publishingOrg":null,"publicationYear":2024,"doi":"10.1056/NEJMoa2403347","pubmedId":"38785209","jurisdiction":null,"dateAccessed":"2026-09-08T17:41:50.436Z","editorialNotes":"AI-assisted evidence synthesis; Owner-authorized governed semaglutide corpus expansion on 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-semaglutide-reference-corpus-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1056/NEJMoa2403347","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T17:41:50.436Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:semaglutide-reference-corpus:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"finding":"Semaglutide reduced the risk of the prespecified major kidney-disease composite outcome versus placebo in the FLOW population.","summary":"FLOW randomized 3,533 patients with type 2 diabetes and chronic kidney disease to weekly semaglutide 1.0 mg or placebo. The primary kidney-disease composite risk was lower with semaglutide, and the trial was stopped early after prespecified interim efficacy criteria were met.","population":"Patients with type 2 diabetes and chronic kidney disease","sampleSize":"3533","limitations":["Early stopping can affect effect-size estimation; findings apply to patients with type 2 diabetes and chronic kidney disease receiving the studied regimen."],"studyDesign":"Randomized double-blind placebo-controlled kidney outcomes trial","sourceStrength":{"note":"Automated baseline based on evidence tier; full-text risk-of-bias review may revise it","grade":"A","score":90,"version":"WPF-ESR-1.0","provisional":true}},"provenancePayload":{"doi":"10.1056/NEJMoa2403347","pmid":"38785209","reviewBatch":"semaglutide-reference-corpus-2026-09-08"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"92d8b1ea-d437-4846-ae33-f27bd5ddfbd8","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/37385278/","evidenceTier":"phase_3","summary":"OASIS 1 randomized 667 adults without type 2 diabetes to once-daily oral semaglutide 50 mg or placebo for 68 weeks. 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Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"A V Ivanov; I I Bobyntsev; O M Shepeleva; A A Kryukov; L A Andreeva; N F Myasoedov","publishingOrg":"Bulletin of experimental biology and medicine","publicationYear":2017,"doi":"10.1007/s10517-017-3748-4","pubmedId":"28577097","jurisdiction":null,"dateAccessed":"2026-09-09T11:41:46.836Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1007/s10517-017-3748-4","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:41:46.836Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"mechanistic","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article"},"provenancePayload":{"doi":"10.1007/s10517-017-3748-4","pmid":"28577097","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:41:46.836Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"19fbe397-b63f-5152-938b-f18990cece78","peptideId":"addc933f-2e6f-42f7-9686-2c1f6da5e728","title":"Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/40692165/","evidenceTier":"animal","summary":"PubMed-indexed journal article examining semax peptide targets the μ opioid receptor gene oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice. 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Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Ivan B Filippenkov; Vasily V Stavchansky; Alina E Denisova; Vadim V Yuzhakov; Larisa E Sevan'kaeva; Olga Y Sudarkina; Veronika G Dmitrieva; Leonid V Gubsky; Nikolai F Myasoedov; Svetlana A Limborska; Lyudmila V Dergunova","publishingOrg":"Genes","publicationYear":2020,"doi":"10.1126/scitranslmed.aaf8732","pubmedId":"32580520","jurisdiction":null,"dateAccessed":"2026-09-09T11:41:46.836Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1126/scitranslmed.aaf8732","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:41:46.836Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"animal_in_vivo","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article; Research Support, Non-U.S. Gov't"},"provenancePayload":{"doi":"10.1126/scitranslmed.aaf8732","pmid":"32580520","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:41:46.836Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"c4841809-5424-5e83-98b1-e310970a3374","peptideId":"addc933f-2e6f-42f7-9686-2c1f6da5e728","title":"[Evolution of the stress concept].","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/19140465/","evidenceTier":"observational","summary":"PubMed-indexed english abstract; journal article; review examining [evolution of the stress concept]. 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Machine-staged source candidate; findings and limitations require accountable review before publication.","authors":"Nataliya Yu Glazova; Daria M Manchenko; Maria A Volodina; Svetlana A Merchieva; Ludmila A Andreeva; Vladimir S Kudrin; Nikolai F Myasoedov; Natalia G Levitskaya","publishingOrg":"Neuropeptides","publicationYear":2021,"doi":"10.1016/j.npep.2020.102114","pubmedId":"33418449","jurisdiction":null,"dateAccessed":"2026-09-09T11:41:46.836Z","editorialNotes":"Machine-staged candidate; no human approval asserted.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":null,"machineActor":"codex-governed-profile-batch-10-2026-09-09","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/j.npep.2020.102114","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-09T11:41:46.836Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":null,"evidenceLane":"animal_in_vivo","extractionPayload":{"sourceStrength":{"grade":"C","version":"WPF-ESR-1.0","provisional":true},"publicationTypes":"Journal Article"},"provenancePayload":{"doi":"10.1016/j.npep.2020.102114","pmid":"33418449","provider":"NCBI PubMed"},"validationGates":{"pmidResolved":true,"humanReviewed":false,"identityResolved":true,"publicationApproved":false},"engineState":"candidate","engineRunId":null,"createdAt":"2026-09-09T11:41:46.836Z","updatedAt":"2026-09-09T19:33:05.147Z"},{"id":"57fd7f9a-a078-525e-a934-3ca78437995d","peptideId":"addc933f-2e6f-42f7-9686-2c1f6da5e728","title":"[Nootropic and analgesic effects of Semax following different routes of administration].","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/21268834/","evidenceTier":"observational","summary":"PubMed-indexed english abstract; journal article examining [nootropic and analgesic effects of semax following different routes of administration]. 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Long-term systemic safety, immunogenicity, angiogenic consequences, interactions, and product-quality risks remain unresolved.","archiveSummaryNote":"The archive deliberately distinguishes TB-500 from full-length thymosin beta-4 and records analytical, preclinical, human, regulatory, and anti-doping sources in separate evidence lanes.","openQuestionsText":"What molecular entity is present in products labeled TB-500? 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METHODS: AAV-Tbeta(4) was prepared and intracolonically used to mediate the secretory …","authors":"Zheng XY, Lv YF, Li S, Li Q, Zhang QN, Zhang XT, Hao ZM.","publishingOrg":null,"publicationYear":2017,"doi":"10.3748/wjg.v23.i2.242","pubmedId":"28127198","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. 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Formulation, device, labeling, eligibility, duration, and safety requirements govern; authorization must not be generalized to unapproved products or uses.","sourceTitle":"FDA Drugs@FDA — BONSITY NDA 211939","sourceUrl":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=211939","dateChecked":"2026-09-10T00:37:11.517Z","reviewDueAt":"2026-12-09T00:37:11.517Z","enteredById":null,"reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","publicationStatus":"published","factualObservationId":null,"createdAt":"2026-09-10T00:37:11.517Z","updatedAt":"2026-09-10T00:43:54.235Z"}]},{"id":"e0362116-0ace-4898-bf44-bc5eca4e263a","slug":"tesamorelin","commonName":"Tesamorelin","alternativeNames":["Egrifta","Egrifta SV","TH9507"],"category":"Growth hormone-releasing hormone analog","mechanismSummary":"Tesamorelin is a stabilized N-terminally modified analog of the 44-amino-acid human growth hormone–releasing hormone. It activates pituitary GHRH receptors, increasing endogenous growth-hormone release and downstream IGF-1 signaling. In the labeled population this pathway reduces visceral adipose tissue; it is not a general weight-loss mechanism.","evidenceQualitySummary":"Evidence is strongest for reducing excess abdominal fat in adults with HIV-associated lipodystrophy: FDA approval is supported by randomized phase 3 trials. Smaller randomized studies report hepatic-fat reductions in selected people with HIV, while cognition and anti-aging uses remain investigational.","safetyConcernsSummary":"Current US labeling addresses active malignancy, disruption of the hypothalamic-pituitary axis, pregnancy, hypersensitivity, elevated IGF-1, fluid retention, glucose intolerance or diabetes, and injection-site reactions. Safety depends on the labeled product, indication, patient factors, and monitoring.","archiveSummaryNote":"Governed corpus spanning FDA labeling, pivotal and extension trials, liver-fat studies, and a controlled cognition study. Approved and investigational findings are separated.","openQuestionsText":"Long-term outcomes beyond body-composition surrogates; durability after discontinuation; cardiometabolic outcomes; broader applicability; and whether liver or cognitive signals translate into durable clinical benefit.","active":true,"createdAt":"2026-08-18T17:25:08.156Z","updatedAt":"2026-09-09T00:27:28.350Z","entityClass":"peptide_analog","entityClassSource":"human_reviewed","entityClassReviewed":true,"entityClassReviewedBy":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","entityClassReviewedAt":"2026-09-09T00:27:28.350Z","registryStatus":"canonical","registryTier":null,"acquisitionEnabled":true,"publicationState":"published","editorialState":"published","chemistry":{"id":"eca5eb38-8bb7-4fa7-804c-96045c6c405a","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","molecularFormula":"C221H366N72O67S","molecularWeight":5135.9,"aminoAcidSequence":null,"smiles":null,"inchi":null,"inchikey":null,"structureImageUrl":null,"createdAt":"2026-09-08T22:50:27.254Z","updatedAt":"2026-09-08T22:50:27.254Z"},"citations":[{"id":"631691e11107bcc7ae45dbd10992f51e","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"Safety and metabolic effects of tesamorelin, a growth hormone-releasing factor analogue, in patients with type 2 diabetes: A randomized, placebo-controlled trial.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/28617838/","evidenceTier":"phase_1_2","summary":"Use of growth hormone is associated with side effects, including insulin resistance. The objective of this study was to determine whether tesamorelin, a stabilized growth hormone-releasing hormone analogue, would alter insulin sensitivity or control of diabetes. A 12-week randomized, placebo-controlled study of 53 patients with type 2 diabetes. Three treatment groups: placebo, 1 and 2 mg tesamorelin. Fasting glucose, glucose and insulin from oral glucose tolerance test, glycosylated hemoglobin (HbA1c), home blood glucose, insulin-like growth factor-1, and lipids. Relative insulin response following oral ingestion of glucose. No significant differences were observed between groups in...","authors":"David R Clemmons, Sam Miller, Jean-Claude Mamputu","publishingOrg":null,"publicationYear":2017,"doi":"10.1371/journal.pone.0179538","pubmedId":"28617838","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Safety and metabolic effects of tesamorelin, a growth hormone-releasing factor analogue, in patients with type 2 diabetes: A randomized, placebo-controlled trial.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1371/journal.pone.0179538","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":86,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Multicenter Study","Randomized Controlled Trial"]},"provenancePayload":{"doi":"10.1371/journal.pone.0179538","pmid":"28617838","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"e05f7bb4471463192334032faa352542","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"Population pharmacokinetic and pharmacodynamic analysis of tesamorelin in HIV-infected patients and healthy subjects.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/25895899/","evidenceTier":"phase_1_2","summary":"The objective of this analysis was to characterize the time course of selected pharmacodynamic (PD) markers of tesamorelin: growth hormone (GH) and insulin-like growth factor (IGF-1) concentrations in HIV-infected patients and healthy volunteers. A total of 41 subjects in Phase I trials receiving subcutaneous daily doses of 1 or 2 mg of tesamorelin during 14 consecutive days were included in this analysis. A previous pharmacokinetic (PK) model of tesamorelin was used as the input function for the PD model of GH. Tesamorelin was hypothesized to stimulate the secretion of GH in an \"episodic\" manner, i.e., for a finite duration of time. The resulting PK/PD model of GH was used to describe...","authors":"Mario González-Sales, Olivier Barrière, Pierre Olivier Tremblay, Fahima Nekka, Jean-Claude Mamputu, Sylvie Boudreault, Mario Tanguay","publishingOrg":null,"publicationYear":2015,"doi":"10.1007/s10928-015-9416-2","pubmedId":"25895899","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Population pharmacokinetic and pharmacodynamic analysis of tesamorelin in HIV-infected patients and healthy subjects.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1007/s10928-015-9416-2","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":86,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Clinical Trial, Phase I","Journal Article","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1007/s10928-015-9416-2","pmid":"25895899","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"7e9381928b6032f155be746e25be8769","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/18690162/","evidenceTier":"phase_1_2","summary":"Treatment of HIV patients with daily tesamorelin, a growth hormone-releasing factor analogue, for 26 weeks resulted in a significant decrease in visceral adipose tissue (VAT) and improvement in lipids. The objective of the 26-week extension phase was to evaluate long-term safety and effects of tesamorelin. HIV patients with central fat accumulation in the context of antiretroviral therapy were randomized to tesamorelin 2 mg (n = 273) or placebo (n = 137) s.c. daily for 26 weeks. At week 26, patients originally on tesamorelin were rerandomized to 2 mg tesamorelin (T-T group, n = 154) or placebo (T-P group, n = 50), whereas patients originally on placebo were switched to tesamorelin (P-T...","authors":"Julian Falutz, Soraya Allas, Jean-Claude Mamputu, Diane Potvin, Donald Kotler, Michael Somero, Daniel Berger, Stephen Brown","publishingOrg":null,"publicationYear":2008,"doi":"10.1097/QAD.0b013e32830a5058","pubmedId":"18690162","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1097/qad.0b013e32830a5058","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":86,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Randomized Controlled Trial","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1097/QAD.0b013e32830a5058","pmid":"18690162","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"20d6e923c8ba0e2e976ca2ff7526963f","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/26457580/","evidenceTier":"phase_1_2","summary":"Tesamorelin, a synthetic analog of human growth hormone-releasing factor, decreases visceral adipose tissue (VAT) in human immunodeficiency virus (HIV)-infected patients with lipodystrophy. 1) To evaluate the utility of patient characteristics and validated disease-risk scores, namely indicator variables for the metabolic syndrome defined by the International Diabetes Federation (MetS-IDF) or the National Cholesterol Education Program (MetS-NCEP) and the Framingham Risk Score (FRS), as predictors of VAT reduction during tesamorelin therapy at 3 and 6 months, and 2) To explore the characteristics of patients who reached a threshold of VAT <140 cm2, a level associated with lower risk of...","authors":"Alexandra Mangili, Julian Falutz, Jean-Claude Mamputu, Miganush Stepanians, Brooke Hayward","publishingOrg":null,"publicationYear":2015,"doi":"10.1371/journal.pone.0140358","pubmedId":"26457580","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1371/journal.pone.0140358","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":86,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Randomized Controlled Trial","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1371/journal.pone.0140358","pmid":"26457580","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"5b865ba9c87443cab3cf931ab8cbddbb","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/22495074/","evidenceTier":"phase_3","summary":"Tesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue (VAT) by 15%-20% over 6-12 months in individuals with human immunodeficiency virus (HIV)-associated abdominal adiposity, but it is unknown whether VAT reduction is directly associated with endocrine and metabolic changes. In 2 phase III, randomized, double-blind studies, men and women with HIV-associated abdominal fat accumulation were randomly assigned (ratio, 2:1) to receive tesamorelin or placebo for 26 weeks. At week 26, patients initially receiving tesamorelin were randomly assigned to continue receiving tesamorelin or to receive placebo for an additional 26 weeks. In per-protocol analysis of...","authors":"Takara L Stanley, Julian Falutz, Christian Marsolais, Josée Morin, Graziella Soulban, Jean-Claude Mamputu, Hani Assaad, Ralph Turner","publishingOrg":null,"publicationYear":2012,"doi":"10.1093/cid/cis251","pubmedId":"22495074","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1093/cid/cis251","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":91,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Clinical Trial, Phase III","Journal Article","Randomized Controlled Trial","Research Support, N.I.H., Extramural","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1093/cid/cis251","pmid":"22495074","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"9775312ff3487c849a1afe1135d3b5a4","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults with HIV.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/31237318/","evidenceTier":"phase_1_2","summary":"Tesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue in people living with HIV, however, the effects on skeletal muscle fat and area are unknown. The goals of this exploratory secondary analysis were to determine the effects of tesamorelin on muscle quality (density) and quantity (area). Secondary, exploratory analysis of two previously completed randomized (2:1), clinical trials. U.S. and Canadian sites. People living with HIV and with abdominal obesity. Tesamorelin participants were restricted to responders (visceral adipose tissue decrease ≥8%). Tesamorelin or placebo. Computed tomography scans (at L4-L5) were used to quantify total and lean...","authors":"S Adrian, A Scherzinger, A Sanyal, J E Lake, J Falutz, M P Dubé, T Stanley, S Grinspoon","publishingOrg":null,"publicationYear":2019,"doi":"10.14283/jfa.2018.45","pubmedId":"31237318","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults with HIV.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.14283/jfa.2018.45","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":86,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Randomized Controlled Trial"]},"provenancePayload":{"doi":"10.14283/jfa.2018.45","pmid":"31237318","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"efc6ca28be7c106c2529f780fb8174cd","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"The effects of tesamorelin on phosphocreatine recovery in obese subjects with reduced GH.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/24178787/","evidenceTier":"phase_1_2","summary":"Few studies have assessed the relationship between GH and mitochondrial function. The objective of this study was to determine the effects of improving IGF-I using a GHRH analog, tesamorelin, on mitochondrial function assessed by phosphocreatine (PCr) recovery using (31)P magnetic resonance spectroscopy in obese adults with reduced GH. A total of 39 obese men and women with reduced GH secretion as determined by GHRH-arginine stimulation tests underwent magnetic resonance spectroscopy as part of a 12-month, double-blind, randomized, placebo-controlled trial comparing tesamorelin vs placebo. PCr recovery after submaximal exercise was assessed at baseline and at 12 months. At baseline,...","authors":"Hideo Makimura, Caitlin A Murphy, Meghan N Feldpausch, Steven K Grinspoon","publishingOrg":null,"publicationYear":2014,"doi":"10.1210/jc.2013-3436","pubmedId":"24178787","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning The effects of tesamorelin on phosphocreatine recovery in obese subjects with reduced GH.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1210/jc.2013-3436","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":86,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Randomized Controlled Trial","Research Support, N.I.H., Extramural","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1210/jc.2013-3436","pmid":"24178787","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"36a96cceb20abe815cd2175b097c06e4","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"Effects of tesamorelin on inflammatory markers in HIV patients with excess abdominal fat: relationship with visceral adipose reduction.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/21516030/","evidenceTier":"phase_3","summary":"To report the effects of tesamorelin, a growth hormone-releasing hormone analogue, on inflammatory and fibrinolytic markers and to relate these effects to changes in visceral adipose tissue (VAT). Four hundred and ten HIV-infected patients with abdominal adiposity were randomized to 2 mg tesamorelin (n = 273) or placebo (n = 137) subcutaneously daily for 26 weeks. Circulating plasminogen activator inhibitor-1 (PAI-1) antigen, tissue plasminogen activator (tPA) antigen, C-reactive protein (CRP), and adiponectin were assessed. At baseline, VAT was significantly associated with PAI-1 antigen (ρ = 0.36, P < 0.001), tPA antigen (ρ = 0.29, P < 0.001), CRP (ρ = 0.18, P < 0.001), and adiponectin...","authors":"Takara L Stanley, Julian Falutz, Jean-Claude Mamputu, Graziella Soulban, Diane Potvin, Steven K Grinspoon","publishingOrg":null,"publicationYear":2011,"doi":"10.1097/QAD.0b013e328347f3f1","pubmedId":"21516030","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Effects of tesamorelin on inflammatory markers in HIV patients with excess abdominal fat: relationship with visceral adipose reduction.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1097/qad.0b013e328347f3f1","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":91,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Clinical Trial, Phase III","Journal Article","Randomized Controlled Trial","Research Support, N.I.H., Extramural","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1097/QAD.0b013e328347f3f1","pmid":"21516030","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"b209856c429f4e4c025ec39ae61bf4f9","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"Population pharmacokinetic analysis of tesamorelin in HIV-infected patients and healthy subjects.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/25358450/","evidenceTier":"phase_1_2","summary":"Tesamorelin is a synthetic analogue of growth hormone-releasing factor (GRF), which increases basal and pulsatile growth hormone (GH) secretion and subsequently increases insulin-like growth factor (IGF)-1. Limited information is available about the pharmacokinetics of this compound. Consequently, the aim of this study was to characterize the population pharmacokinetics of tesamorelin in HIV-infected patients and healthy subjects. A total of 38 HIV-infected patients and healthy subjects receiving subcutaneous tesamorelin doses of 1 or 2 mg administered daily during 14 consecutive days were included in the analysis. An open one-compartment model with first- and zero-order absorption and...","authors":"Mario González-Sales, Olivier Barrière, Pierre Olivier Tremblay, Fahima Nekka, Jean-Claude Mamputu, Sylvie Boudreault, Mario Tanguay","publishingOrg":null,"publicationYear":2015,"doi":"10.1007/s40262-014-0202-x","pubmedId":"25358450","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Population pharmacokinetic analysis of tesamorelin in HIV-infected patients and healthy subjects.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1007/s40262-014-0202-x","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":86,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Clinical Trial, Phase I","Journal Article","Randomized Controlled Trial","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1007/s40262-014-0202-x","pmid":"25358450","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"da42a663d05ed6438e209dff00bd2868","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"Body composition, hepatic fat, metabolic, and safety outcomes of Tesamorelin, a GHRH analogue, in HIV-associated lipodystrophy: A meta-analysis of randomized controlled trials.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/41545261/","evidenceTier":"observational","summary":"HIV-associated lipodystrophy leads to visceral fat accumulation, metabolic complications, body image concerns, medication non-adherence, and increased cardiovascular risks. We thought to assess the effects of Tesamorelin, a synthetic growth hormone-releasing hormone analogue, that has been proposed as a targeted therapy. We systematically searched PubMed, Embase, Scopus, Web of Science, and CENTRAL through July 2025 for randomized controlled trials (RCTs) evaluating Tesamorelin versus placebo in adults with HIV. Random-effects meta-analysis was applied. Outcomes included changes in body composition, hepatic and metabolic parameters, hormonal markers, and adverse events. Risk of bias was...","authors":"Ahmed Samy Badran, Abdulrhman Helal, Karim Samir Shata, Hazem Ayesh","publishingOrg":null,"publicationYear":2026,"doi":"10.1016/j.orcp.2026.01.002","pubmedId":"41545261","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes meta_analysis evidence concerning Body composition, hepatic fat, metabolic, and safety outcomes of Tesamorelin, a GHRH analogue, in HIV-associated lipodystrophy: A meta-analysis of randomized controlled trials.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/j.orcp.2026.01.002","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"meta_analysis","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Systematic review and meta-analysis","sourceStrength":{"grade":"A","score":83,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Meta-Analysis","Journal Article","Systematic Review"]},"provenancePayload":{"doi":"10.1016/j.orcp.2026.01.002","pmid":"41545261","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"7cfc30a2673b282c10c15ef5f49f89c7","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"Efficacy and Safety of Tesamorelin in People Living With HIV (PLWH) With Lipodystrophy: A Systematic Review and Meta-Analysis.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/42538058/","evidenceTier":"observational","summary":"BackgroundHIV-associated lipodystrophy, a complication of combined antiretroviral therapy (CART), causes significant physical and psychological distress in people living with HIV (PLWH), compromising treatment adherence. Tesamorelin, a growth hormone-releasing hormone (GHRH) analogue, has emerged as a therapeutic option.ObjectiveTo systematically evaluate the efficacy and safety of tesamorelin in HIV-infected individuals with lipodystrophy receiving CART, incorporating GRADE assessment.MethodsWe searched PubMed, https://ClinicalTrials.gov, and Scopus from inception to February 9, 2026, for randomized controlled trials evaluating tesamorelin in HIV-associated lipodystrophy. Mean...","authors":"Aqsa Mohammed Ditta, Ruqaiya Muhammad Naeem, Muhammad Mohsin Sami, Muhammad Abdul Rafey, Hunain Ali, Muhammad Waqar Amjad, Fahad Jahangir, Kehan Ali Rizvi","publishingOrg":null,"publicationYear":2026,"doi":"10.1177/23259582261475549","pubmedId":"42538058","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes meta_analysis evidence concerning Efficacy and Safety of Tesamorelin in People Living With HIV (PLWH) With Lipodystrophy: A Systematic Review and Meta-Analysis.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1177/23259582261475549","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"meta_analysis","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Systematic review and meta-analysis","sourceStrength":{"grade":"A","score":83,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Systematic Review","Meta-Analysis"]},"provenancePayload":{"doi":"10.1177/23259582261475549","pmid":"42538058","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"fd0a86a1a7e5d7344537484055a60b05","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"Spotlight on tesamorelin in HIV-associated lipodystrophy.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/22050344/","evidenceTier":"insufficient","summary":"Tesamorelin (Egrifta™) is a synthetic analog of human growth hormone-releasing hormone (also known as growth hormone-releasing factor) that stimulates the synthesis and release of endogenous growth hormone. It is the first and, so far, only treatment indicated for the reduction of excess abdominal fat in patients with HIV-associated lipodystrophy. This article reviews the pharmacological properties, clinical efficacy and tolerability of tesamorelin in patients with HIV-associated central fat accumulation. Subcutaneous tesamorelin was effective in reducing visceral adipose tissue (VAT), but did not affect subcutaneous adipose tissue to a clinically significant extent in two 26-week, well...","authors":"Sohita Dhillon","publishingOrg":null,"publicationYear":2011,"doi":"10.2165/11208290-000000000-00000","pubmedId":"22050344","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Spotlight on tesamorelin in HIV-associated lipodystrophy.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.2165/11208290-000000000-00000","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Narrative or scoped review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.2165/11208290-000000000-00000","pmid":"22050344","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"b41c9754b7ba255b6d62ff2a72815cd1","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"Drug evaluation: tesamorelin, a synthetic human growth hormone releasing factor.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/17086939/","evidenceTier":"insufficient","summary":"Theratechnologies, under license from Valeant, is developing tesamorelin as a potential vaccine adjuvant and for the potential treatment of wasting, hip fracture recovery, immune disorders, HIV-related lipodystrophy, sleep maintenance insomnia and mild cognitive impairment. Phase III clinical trials for the treatment of HIV-associated lipodystrophy and phase II clinical trials for sleep disorder, chronic obstructive pulmonary disorder, hip fracture and immune system dysfunction are underway. Phase II trials are also assessing the influenza vaccination immune response and cognitive effects of tesamorelin.","authors":"Brian Tomlinson","publishingOrg":null,"publicationYear":2006,"doi":null,"pubmedId":"17086939","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Drug evaluation: tesamorelin, a synthetic human growth hormone releasing factor.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"pmid:17086939","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Narrative or scoped review","sourceStrength":{"grade":"C","score":63,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":null,"pmid":"17086939","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"8ef7abb51f1c3dfc38d6e6a2162b05df","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"Efficacy and safety of tesamorelin in people with HIV on integrase inhibitors.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/38905488/","evidenceTier":"phase_1_2","summary":"Tesamorelin is the only FDA-approved therapy to treat abdominal fat accumulation in people with HIV (PWH). Phase III clinical trials were conducted prior to the introduction of integrase inhibitors (INSTIs), which are now a mainstay of HIV antiretroviral therapy. We leveraged a randomized double-blind trial of 61 PWH and metabolic dysfunction-associated steatotic liver disease to evaluate the efficacy and safety of tesamorelin 2 mg once daily vs. identical placebo among participants on INSTI-based regimens at baseline. In the parent clinical trial, visceral fat cross-sectional area, hepatic fat fraction, and trunk-to-appendicular fat ratio were quantified using magnetic resonance...","authors":"Samuel C Russo, Mollie W Ockene, Allison K Arpante, Julia E Johnson, Hang Lee, Mabel Toribio, Takara L Stanley, Colleen M Hadigan","publishingOrg":null,"publicationYear":2024,"doi":"10.1097/QAD.0000000000003965","pubmedId":"38905488","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Efficacy and safety of tesamorelin in people with HIV on integrase inhibitors.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1097/qad.0000000000003965","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":86,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Randomized Controlled Trial","Research Support, Non-U.S. Gov't","Research Support, N.I.H., Extramural"]},"provenancePayload":{"doi":"10.1097/QAD.0000000000003965","pmid":"38905488","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"85e4f539659adfa313482d3a09c35085","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/32701508/","evidenceTier":"phase_1_2","summary":"Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity among people living with HIV that has a more aggressive course than NAFLD among the general population. In a recent randomized placebo-controlled trial, we demonstrated that the growth hormone-releasing hormone analog tesamorelin reduced liver fat and prevented fibrosis progression in HIV-associated NAFLD over 1 year. As such, tesamorelin is the first strategy that has shown to be effective against NAFLD among the population with HIV. The current study leveraged paired liver biopsy specimens from this trial to identify hepatic gene pathways that are differentially modulated by tesamorelin versus placebo. Using gene set...","authors":"Lindsay T Fourman, James M Billingsley, George Agyapong, Shannan J Ho Sui, Meghan N Feldpausch, Julia Purdy, Isabel Zheng, Chelsea S Pan","publishingOrg":null,"publicationYear":2020,"doi":"10.1172/jci.insight.140134","pubmedId":"32701508","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1172/jci.insight.140134","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":86,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Randomized Controlled Trial","Research Support, N.I.H., Extramural","Research Support, N.I.H., Intramural","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1172/jci.insight.140134","pmid":"32701508","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"97da563802bc798d556939708236a85d","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"Effects of Tesamorelin on Neurocognitive Impairment in Persons With HIV and Abdominal Obesity.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/39813152/","evidenceTier":"phase_1_2","summary":"In people with HIV who are virally suppressed with antiretroviral therapy, abdominal obesity (AO) is linked to neurocognitive impairment (NCI), potentially due to visceral adiposity, inflammation, and reduced insulin-like growth factor 1 (IGF-1). Tesamorelin, a growth hormone-releasing hormone, reduces AO and increases IGF-1, suggesting that it might mitigate NCI in people with HIV and viral suppression. This 6-month phase 2 randomized open-label clinical trial compared tesamorelin vs standard of care (SOC) for NCI in people with HIV who were virally suppressed and abdominally obese (elevated waist circumference [WC]). Exclusions included conditions other than HIV causing NCI, active...","authors":"Ronald J Ellis, Florin Vaida, Keren Hu, Michael Dube, Brook Henry, Felicia Chow, Robert K Heaton, Daniel Lee","publishingOrg":null,"publicationYear":2025,"doi":"10.1093/infdis/jiaf012","pubmedId":"39813152","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Effects of Tesamorelin on Neurocognitive Impairment in Persons With HIV and Abdominal Obesity.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1093/infdis/jiaf012","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":86,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Clinical Trial, Phase II","Journal Article","Multicenter Study","Randomized Controlled Trial"]},"provenancePayload":{"doi":"10.1093/infdis/jiaf012","pmid":"39813152","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"1c0bdc3af91dfbdd0e0e29da3074bc43","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"Tesamorelin: a review of its use in the management of HIV-associated lipodystrophy.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/21668043/","evidenceTier":"insufficient","summary":"Tesamorelin (Egrifta™) is a synthetic analogue of human growth hormone-releasing hormone (also known as growth hormone-releasing factor) that stimulates the synthesis and release of endogenous growth hormone. It is the first and, so far, only treatment indicated for the reduction of excess abdominal fat in patients with HIV-associated lipodystrophy. This article reviews the pharmacological properties, clinical efficacy and tolerability of tesamorelin in patients with HIV-associated central fat accumulation. Subcutaneous tesamorelin was effective in reducing visceral adipose tissue (VAT), but did not affect subcutaneous adipose tissue to a clinically significant extent in two 26-week,...","authors":"Sohita Dhillon","publishingOrg":null,"publicationYear":2011,"doi":"10.2165/11202240-000000000-00000","pubmedId":"21668043","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Tesamorelin: a review of its use in the management of HIV-associated lipodystrophy.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.2165/11202240-000000000-00000","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Narrative or scoped review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.2165/11202240-000000000-00000","pmid":"21668043","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"0e9df998fb8b2de550f8360bdfa26ea1","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"Tesamorelin, a human growth hormone releasing factor analogue.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/19243281/","evidenceTier":"insufficient","summary":"The combination of clinical effectiveness with a variety of adverse side effects from the use of recombinant human growth hormone (rhGH) in therapy for growth hormone (GH)-deficient disorders has led to the development of human growth hormone releasing factor (GFR) analogues, which may be better tolerated. Tesamorelin, a synthetic GFR, has been developed as a potential treatment for a variety of conditions that may be associated with a relative deficiency of GH including HIV-related lipodystrophy. This article reviews the development of tesamorelin and its purported role in HIV-related lipodystrophy and other potential indications. Relevant articles and abstracts were obtained from...","authors":"Ying Wang, Brian Tomlinson","publishingOrg":null,"publicationYear":2009,"doi":"10.1517/13543780802707658","pubmedId":"19243281","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Tesamorelin, a human growth hormone releasing factor analogue.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1517/13543780802707658","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Narrative or scoped review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.1517/13543780802707658","pmid":"19243281","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"ae65f06647aff793347592f6f6341537","peptideId":"e0362116-0ace-4898-bf44-bc5eca4e263a","title":"Tesamorelin: a growth hormone-releasing factor analogue for HIV-associated lipodystrophy.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/22298602/","evidenceTier":"insufficient","summary":"To evaluate the efficacy and safety of tesamorelin, a growth hormone releasing factor analogue approved by the Food and Drug Administration in November 2010 for the treatment of lipodystrophy associated with HIV infection. Literature was obtained through MEDLINE (1948-November 2011) and International Pharmaceutical Abstracts (1970-October 2011) using the search terms tesamorelin, TH9507, growth hormone releasing factor, and HIV-associated lipodystrophy syndrome. Additional publications were obtained through review of references within primary literature publications as well as pertinent Web sites. All articles published in English identified from the data sources were evaluated and all...","authors":"Linda M Spooner, Jacqueline L Olin","publishingOrg":null,"publicationYear":2012,"doi":"10.1345/aph.1Q629","pubmedId":"22298602","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Tesamorelin: a growth hormone-releasing factor analogue for HIV-associated lipodystrophy.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1345/aph.1q629","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tesamorelin:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; 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Primary outcomes included...","authors":"Lauren Wilson, Zhenxiang Zhao, Victoria Divino, Matthew Bassan, Bríain Ó Hartaigh, Signe Stensen, Kerem Ozer","publishingOrg":null,"publicationYear":2026,"doi":"10.1111/dom.70436","pubmedId":"41491349","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_observational evidence concerning Semaglutide and tirzepatide effects on cardiovascular outcomes in people with overweight or obesity in the real world (STEER).","supportNature":"contextualizes","qualification":"Observational evidence is vulnerable to confounding, selection bias, exposure misclassification, and incomplete follow-up.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1111/dom.70436","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tirzepatide:expansion:2026-09-08","evidenceLane":"human_observational","extractionPayload":{"limitations":["Observational evidence is vulnerable to confounding, selection bias, exposure misclassification, and incomplete follow-up."],"studyDesign":"Human observational study","sourceStrength":{"grade":"B","score":77,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Observational Study"]},"provenancePayload":{"doi":"10.1111/dom.70436","pmid":"41491349","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"360fc889a0b9a4b2894e0bc8c6dd4590","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/36050763/","evidenceTier":"insufficient","summary":"Tirzepatide is the first dual GIP/GLP-1 receptor co-agonist approved for the treatment of type 2 diabetes in the USA, Europe, and the UAE. Tirzepatide is an acylated peptide engineered to activate the GIP and GLP-1 receptors, key mediators of insulin secretion that are also expressed in regions of the brain that regulate food intake. Five clinical trials in type 2-diabetic subjects (SURPASS 1-5) have shown that tirzepatide at 5-15 mg per week reduces both HbA1c (1.24 to 2.58%) and body weight (5.4-11.7 kg) by amounts unprecedented for a single agent. A sizable proportion of patients (23.0 to 62.4%) reached an HbA1c of < 5.7% (which is the upper limit of the normal range indicating...","authors":"Michael A Nauck, David A D'Alessio","publishingOrg":null,"publicationYear":2022,"doi":"10.1186/s12933-022-01604-7","pubmedId":"36050763","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1186/s12933-022-01604-7","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tirzepatide:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Narrative or scoped review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1186/s12933-022-01604-7","pmid":"36050763","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"791bad518785ac518f9d9b50ea41f952","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Tirzepatide for overweight and obesity management.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/39632534/","evidenceTier":"insufficient","summary":"Tirzepatide is a once-weekly dual agonist, acting on glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. It is approved at the same doses (5, 10 and 15 mg) for both type 2 diabetes (T2D) and chronic weight management. Following a search in PubMed, clinicaltrials.gov, conference abstracts and Lilly website, we review herein the global phase 3 SURMOUNT program on tirzepatide's safety and efficacy for chronic weight management. Additionally, we discuss findings from the regional SURMOUNT-CN and SURMOUNT-J trials (in East-Asian populations) and the phase 2 SYNERGY-NASH, phase 3 SURMOUNT-OSA and SUMMIT studies on tirzepatide's impact on...","authors":"Malak Hamza, Dimitris Papamargaritis, Melanie J Davies","publishingOrg":null,"publicationYear":2025,"doi":"10.1080/14656566.2024.2436595","pubmedId":"39632534","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Tirzepatide for overweight and obesity management.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1080/14656566.2024.2436595","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tirzepatide:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Narrative or scoped review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.1080/14656566.2024.2436595","pmid":"39632534","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"a9f6108d5f132db3d1278da5405a49c9","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes and obesity: a systematic review and meta-analysis.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/37908750/","evidenceTier":"observational","summary":"A systematic review and meta-analysis was conducted to synthesize the available data from clinical trials and assess the safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes (T2D) and obesity. A systematic search was conducted in three electronic databases, namely Embase, PubMed, and the Cochrane Library, up until March 1, 2023, to identify randomized controlled trials (RCTs) comparing tirzepatide to either placebo or active hypoglycemic drugs in individuals with T2D and obesity. Heterogeneity was assessed using the I2 value and Cochran's Q test, and a fixed effects model was employed to estimate the safety profile of tirzepatide. The safety...","authors":"Qingyue Zeng, Jiao Xu, Xingyu Mu, Yi Shi, Hong Fan, Shuangqing Li","publishingOrg":null,"publicationYear":2023,"doi":"10.3389/fendo.2023.1214334","pubmedId":"37908750","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes meta_analysis evidence concerning Safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes and obesity: a systematic review and meta-analysis.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.3389/fendo.2023.1214334","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tirzepatide:expansion:2026-09-08","evidenceLane":"meta_analysis","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Systematic review and meta-analysis","sourceStrength":{"grade":"A","score":83,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Meta-Analysis","Systematic Review","Research Support, Non-U.S. Gov't","Journal Article"]},"provenancePayload":{"doi":"10.3389/fendo.2023.1214334","pmid":"37908750","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"53beab9e77e939095585e95fbdb07624","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Anti-inflammatory effects of tirzepatide: a systematic review and meta-analysis.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/41032183/","evidenceTier":"observational","summary":"Tirzepatide, a dual GIP and GLP-1 receptor agonist, has shown significant metabolic benefits and weight reduction, but its anti-inflammatory effects have been less studied. This study was conducted in accordance with PRISMA guidelines, including observational (cohort) studies and randomized clinical trials that evaluated tirzepatide use and reported percentage changes in high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). A random-effects model was used. Seven randomized clinical trials and one observational study were included (six studies were eligible for meta-analysis). Compared to placebo, tirzepatide reduced hsCRP (mean difference [MD]: -32.9; 95% confidence...","authors":"Walter Masson, Martín Lobo, Juan P Nogueira, Leandro Barbagelata, Pedro Touzas, Juan P Frías","publishingOrg":null,"publicationYear":2026,"doi":"10.1007/s11154-025-09991-4","pubmedId":"41032183","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes meta_analysis evidence concerning Anti-inflammatory effects of tirzepatide: a systematic review and meta-analysis.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1007/s11154-025-09991-4","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tirzepatide:expansion:2026-09-08","evidenceLane":"meta_analysis","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Systematic review and meta-analysis","sourceStrength":{"grade":"A","score":83,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Systematic Review","Meta-Analysis"]},"provenancePayload":{"doi":"10.1007/s11154-025-09991-4","pmid":"41032183","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"14e763cb254b44b88d7551e6733231e7","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Tirzepatide: A Systematic Update.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/36498958/","evidenceTier":"observational","summary":"Tirzepatide is a new molecule capable of controlling glucose blood levels by combining the dual agonism of Glucose-Dependent Insulinotropic Polypeptide (GIP) and Glucagon-Like Peptide-1 (GLP-1) receptors. GIP and GLP1 are incretin hormones: they are released in the intestine in response to nutrient intake and stimulate pancreatic beta cell activity secreting insulin. GIP and GLP1 also have other metabolic functions. GLP1, in particular, reduces food intake and delays gastric emptying. Moreover, Tirzepatide has been shown to improve blood pressure and to reduce Low-Density Lipoprotein (LDL) cholesterol and triglycerides. Tirzepatide efficacy and safety were assessed in a phase III SURPASS...","authors":"Imma Forzano, Fahimeh Varzideh, Roberta Avvisato, Stanislovas S Jankauskas, Pasquale Mone, Gaetano Santulli","publishingOrg":null,"publicationYear":2022,"doi":"10.3390/ijms232314631","pubmedId":"36498958","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Tirzepatide: A Systematic Update.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.3390/ijms232314631","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tirzepatide:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Systematic review","sourceStrength":{"grade":"B","score":79,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Systematic Review"]},"provenancePayload":{"doi":"10.3390/ijms232314631","pmid":"36498958","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"57a5b23dbbd0ec8304b003d1e1c0d92e","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/35133415/","evidenceTier":"phase_3","summary":"The effects of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, as an addition to insulin glargine for treatment of type 2 diabetes have not been described. To assess the efficacy and safety of tirzepatide added to insulin glargine in patients with type 2 diabetes with inadequate glycemic control. Randomized phase 3 clinical trial conducted at 45 medical research centers and hospitals in 8 countries (enrollment from August 30, 2019, to March 20, 2020; follow-up completed January 13, 2021) in 475 adults with type 2 diabetes and inadequate glycemic control while treated with once-daily insulin glargine with or without metformin....","authors":"Dominik Dahl, Yukiko Onishi, Paul Norwood, Ruth Huh, Ross Bray, Hiren Patel, Ángel Rodríguez","publishingOrg":null,"publicationYear":2022,"doi":"10.1001/jama.2022.0078","pubmedId":"35133415","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1001/jama.2022.0078","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tirzepatide:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":91,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Clinical Trial, Phase III","Comparative Study","Journal Article","Randomized Controlled Trial","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1001/jama.2022.0078","pmid":"35133415","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"03c5486277435445db8f18b2f0ed03fb","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/35210595/","evidenceTier":"observational","summary":"Tirzepatide is a novel, once weekly, dual GIP/GLP-1 receptor agonist and is under development for the treatment of type 2 diabetes (T2D) and obesity. Its association with cardiovascular outcomes requires evaluation. This pre-specified cardiovascular meta-analysis included all seven randomized controlled trials with a duration of at least 26 weeks from the tirzepatide T2D clinical development program, SURPASS. The pre-specified primary objective of this meta-analysis was the comparison of the time to first occurrence of confirmed four-component major adverse cardiovascular events (MACE-4; cardiovascular death, myocardial infarction, stroke and hospitalized unstable angina) between pooled...","authors":"Naveed Sattar, Darren K McGuire, Imre Pavo, Govinda J Weerakkody, Hiroshi Nishiyama, Russell J Wiese, Sophia Zoungas","publishingOrg":null,"publicationYear":2022,"doi":"10.1038/s41591-022-01707-4","pubmedId":"35210595","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes meta_analysis evidence concerning Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis.","supportNature":"contextualizes","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1038/s41591-022-01707-4","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tirzepatide:expansion:2026-09-08","evidenceLane":"meta_analysis","extractionPayload":{"limitations":["Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods."],"studyDesign":"Systematic review and meta-analysis","sourceStrength":{"grade":"A","score":83,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Meta-Analysis","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1038/s41591-022-01707-4","pmid":"35210595","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"16a6309ecfd35b927e9e24c9de267a24","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/41406444/","evidenceTier":"phase_3","summary":"Tirzepatide, a dual incretin agonist of the glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors, has favorable effects on glycemic control and body weight. The effects on cardiovascular outcomes are uncertain. We conducted an active-comparator-controlled, double-blind, noninferiority trial in which patients with type 2 diabetes and atherosclerotic cardiovascular disease were randomly assigned in a 1:1 ratio to receive a weekly subcutaneous injection of tirzepatide (up to 15 mg) or dulaglutide (1.5 mg), an agent that has been shown to reduce the incidence of cardiovascular events. The primary end point was a composite of death from cardiovascular causes,...","authors":"Stephen J Nicholls, Imre Pavo, Deepak L Bhatt, John B Buse, Stefano Del Prato, Steven E Kahn, A Michael Lincoff, Darren K McGuire","publishingOrg":null,"publicationYear":2025,"doi":"10.1056/NEJMoa2505928","pubmedId":"41406444","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1056/nejmoa2505928","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tirzepatide:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":91,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Clinical Trial, Phase III","Equivalence Trial","Journal Article","Multicenter Study"]},"provenancePayload":{"doi":"10.1056/NEJMoa2505928","pmid":"41406444","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"0409db93afc0ee86697892579a0d08d4","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/39996356/","evidenceTier":"phase_3","summary":"We assessed changes in body composition following tirzepatide treatment in a substudy of participants with obesity or overweight from the SURMOUNT-1 trial, overall and post hoc in clinically relevant subgroups. Substudy participants (n = 160 of the 2539 in SURMOUNT-1) underwent dual-energy X-ray absorptiometry (DXA) at baseline and Week 72. Body composition parameters were evaluated by analysis of covariance, logistic regression or Fisher's exact test. Post hoc subgroup analyses were conducted by sex (female or male), age (<50, 50 to <65, or ≥65 years) and total body weight reduction tertiles (≤15.3 kg, >15.3 to ≤25.9 kg, or >25.9 kg). The 160 participants (pooled tirzepatide doses n =...","authors":"Michelle Look, Julia P Dunn, Robert F Kushner, Dachuang Cao, Charles Harris, Theresa Hunter Gibble, Adam Stefanski, Ryan Griffin","publishingOrg":null,"publicationYear":2025,"doi":"10.1111/dom.16275","pubmedId":"39996356","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1111/dom.16275","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tirzepatide:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":91,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Clinical Trial, Phase III","Journal Article","Multicenter Study","Randomized Controlled Trial"]},"provenancePayload":{"doi":"10.1111/dom.16275","pmid":"39996356","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"d96226b75828d379ddbf204522f9e682","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/38976257/","evidenceTier":"observational","summary":"Although tirzepatide and semaglutide were shown to reduce weight in randomized clinical trials, data from head-to-head comparisons in populations with overweight or obesity are not yet available. To compare on-treatment weight loss and rates of gastrointestinal adverse events (AEs) among adults with overweight or obesity receiving tirzepatide or semaglutide labeled for type 2 diabetes (T2D) in a clinical setting. In this cohort study, adults with overweight or obesity receiving semaglutide or tirzepatide between May 2022 and September 2023 were identified using electronic health record (EHR) data linked to dispensing information from a collective of US health care systems. On-treatment...","authors":"Patricia J Rodriguez, Brianna M Goodwin Cartwright, Samuel Gratzl, Rajdeep Brar, Charlotte Baker, Ty J Gluckman, Nicholas L Stucky","publishingOrg":null,"publicationYear":2024,"doi":"10.1001/jamainternmed.2024.2525","pubmedId":"38976257","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_observational evidence concerning Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity.","supportNature":"contextualizes","qualification":"Observational evidence is vulnerable to confounding, selection bias, exposure misclassification, and incomplete follow-up.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1001/jamainternmed.2024.2525","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tirzepatide:expansion:2026-09-08","evidenceLane":"human_observational","extractionPayload":{"limitations":["Observational evidence is vulnerable to confounding, selection bias, exposure misclassification, and incomplete follow-up."],"studyDesign":"Human observational study","sourceStrength":{"grade":"B","score":77,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Observational Study","Comparative Study","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1001/jamainternmed.2024.2525","pmid":"38976257","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"8b5b5767ac7bf5fd01e21d8d75f4392e","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/40353578/","evidenceTier":"phase_3","summary":"Tirzepatide and semaglutide are highly effective medications for obesity management. The efficacy and safety of tirzepatide as compared with semaglutide in adults with obesity but without type 2 diabetes is unknown. In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks. The primary end point was the percent change in weight from baseline to week 72. Key secondary end points included weight reductions of at least 10%, 15%, 20%,...","authors":"Louis J Aronne, Deborah Bade Horn, Carel W le Roux, Wayne Ho, Beverly L Falcon, Elisa Gomez Valderas, Sagar Das, Clare J Lee","publishingOrg":null,"publicationYear":2025,"doi":"10.1056/NEJMoa2416394","pubmedId":"40353578","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1056/nejmoa2416394","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tirzepatide:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":91,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Clinical Trial, Phase III","Comparative Study","Equivalence Trial","Journal Article","Multicenter Study"]},"provenancePayload":{"doi":"10.1056/NEJMoa2416394","pmid":"40353578","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"df2e48cee4fd21f8230cb59cbfbf1594","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Tirzepatide for Weight Reduction in Chinese Adults With Obesity: The SURMOUNT-CN Randomized Clinical Trial.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/38819983/","evidenceTier":"phase_3","summary":"Obesity has become a global public health concern and China has the largest number of affected people worldwide. To assess the efficacy and safety of treatment with tirzepatide for weight reduction in Chinese adults with obesity or overweight and weight-related comorbidities. This randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 29 centers in China from September 2021 to December 2022 included Chinese adults (aged ≥18 years) with a body mass index (BMI) greater than or equal to 28 or greater than or equal to 24 and at least 1 weight-related comorbidity, excluding diabetes. Participants were randomly assigned (1:1:1) to receive once-weekly, subcutaneous...","authors":"Lin Zhao, Zhifeng Cheng, Yibing Lu, Ming Liu, Hong Chen, Min Zhang, Rui Wang, Yuan Yuan","publishingOrg":null,"publicationYear":2024,"doi":"10.1001/jama.2024.9217","pubmedId":"38819983","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Tirzepatide for Weight Reduction in Chinese Adults With Obesity: The SURMOUNT-CN Randomized Clinical Trial.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1001/jama.2024.9217","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tirzepatide:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":91,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Clinical Trial, Phase III","Journal Article","Multicenter Study","Randomized Controlled Trial","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1001/jama.2024.9217","pmid":"38819983","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"bd574d7a17a7ecf86799a849e3cff559","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Tirzepatide for Obesity Treatment and Diabetes Prevention.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/39536238/","evidenceTier":"phase_3","summary":"Obesity is a chronic disease and causal precursor to myriad other conditions, including type 2 diabetes. In an earlier analysis of the SURMOUNT-1 trial, tirzepatide was shown to provide substantial and sustained reductions in body weight in persons with obesity over a 72-week period. Here, we report the 3-year safety outcomes with tirzepatide and its efficacy in reducing weight and delaying progression to type 2 diabetes in persons with both obesity and prediabetes. We performed a phase 3, double-blind, randomized, controlled trial in which 2539 participants with obesity, of whom 1032 also had prediabetes, were assigned in a 1:1:1:1 ratio to receive tirzepatide at a once-weekly dose of 5...","authors":"Ania M Jastreboff, Carel W le Roux, Adam Stefanski, Louis J Aronne, Bruno Halpern, Sean Wharton, John P H Wilding, Leigh Perreault","publishingOrg":null,"publicationYear":2025,"doi":"10.1056/NEJMoa2410819","pubmedId":"39536238","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Tirzepatide for Obesity Treatment and Diabetes Prevention.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1056/nejmoa2410819","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:tirzepatide:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration."],"studyDesign":"Randomized or controlled human clinical trial","sourceStrength":{"grade":"A","score":91,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Randomized Controlled Trial","Clinical Trial, Phase III","Multicenter Study"]},"provenancePayload":{"doi":"10.1056/NEJMoa2410819","pmid":"39536238","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"a8f306ef-d7ec-42e1-962a-d0a79fc5d16e","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2)","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/37385275/","evidenceTier":"phase_3","summary":"In 938 adults with type 2 diabetes, tirzepatide reduced weight more than placebo at 72 weeks; gastrointestinal events were most common.","authors":null,"publishingOrg":null,"publicationYear":2023,"doi":"10.1016/S0140-6736(23)01200-X","pubmedId":"37385275","jurisdiction":null,"dateAccessed":"2026-09-08T17:59:47.986Z","editorialNotes":"AI-assisted synthesis; owner-authorized governed publication 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-reference-corpus-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/S0140-6736(23)01200-X","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T17:59:47.986Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:reference-corpus:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"design":"Randomized double-blind placebo-controlled phase 3 trial.","limitations":["Findings are specific to diabetes, studied doses, eligibility, and duration."],"sourceStrength":{"note":"Automated baseline based on evidence tier; 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gastrointestinal events predominated.","authors":null,"publishingOrg":null,"publicationYear":2021,"doi":"10.1056/NEJMoa2107519","pubmedId":"34170647","jurisdiction":null,"dateAccessed":"2026-09-08T17:59:47.986Z","editorialNotes":"AI-assisted synthesis; owner-authorized governed publication 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":null,"supportNature":null,"qualification":null,"verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-reference-corpus-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1056/NEJMoa2107519","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T17:59:47.986Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:reference-corpus:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"design":"Randomized open-label active-controlled phase 3 trial.","limitations":["Open-label design, one semaglutide dose, and 40-week duration constrain comparison."],"sourceStrength":{"note":"Automated baseline based on evidence tier; 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V1a-receptor activation constricts vascular smooth muscle, V2-receptor activation promotes renal water reabsorption through aquaporin-2 trafficking, and additional receptor signaling contributes to pituitary, hemostatic, and central effects. Pharmaceutical vasopressin is used in tightly defined clinical contexts, notably as an intravenous vasopressor for vasodilatory shock in the United States; endogenous physiology, diagnostic biomarkers, receptor antagonists, analogs, and investigational intranasal research must remain distinct.","evidenceQualitySummary":"The governed 25-source corpus emphasizes randomized trials and systematic reviews of vasopressin in septic and vasoplegic shock, including renal, mortality, hemodynamic, dose, pediatric, cancer, and cardiac-surgery contexts. Separate evidence lanes cover cardiac arrest, portal-variceal bleeding, gynecologic local injection, human vascular pharmacology, and safety. PubMed identities, titles, authorship, publication metadata, DOI/PMID, direct vasopressin relevance, source status, and duplication were verified. Studies of desmopressin, terlipressin, receptor antagonists, or copeptin were excluded from the core therapeutic corpus unless directly necessary for clearly labeled context.","safetyConcernsSummary":"Vasopressin can cause excessive vasoconstriction and ischemia involving cardiac, mesenteric, digital, or cutaneous circulations; reduced cardiac output, arrhythmias, hyponatremia or water-balance disturbances, and extravasation-related injury are additional concerns depending on route and context. Risk varies with shock phenotype, dose, duration, concomitant catecholamines, vascular disease, and monitoring. Local intramyometrial injection and historical gastrointestinal-bleeding or cardiac-arrest protocols are not interchangeable with labeled intravenous vasodilatory-shock use. Canadian and U.S. products cited here differ in routes, indications, formulation, and safety instructions.","archiveSummaryNote":"The strongest therapeutic evidence concerns adjunctive or comparative vasopressin in vasodilatory shock, but trials and meta-analyses do not support treating all shock populations as equivalent. Timing, dose, catecholamine exposure, septic phenotype, cardiac function, pediatric status, and outcome definition materially affect interpretation. Historical and procedural uses are retained to document the breadth and evolution of clinical investigation, not to imply current authorization or preferred practice. Behavioral intranasal research and physiological biomarker studies remain separate from the clinical vasopressor evidence lane.","openQuestionsText":"Which shock phenotypes, timing strategies, and dose ranges provide the best net clinical benefit? Can biomarkers or hemodynamic features identify responders while minimizing ischemic injury? What are the comparative effects on kidney-replacement therapy, arrhythmia, digital or mesenteric ischemia, and long-term patient-centered outcomes? How should evidence differ in septic, post-cardiotomy, pediatric, cancer-associated, and other vasoplegic states? Which historical or local procedural uses remain supported under contemporary safety standards? 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