{"schemaVersion":"wpf-profile-export-v1","exportedAt":"2026-09-18T15:18:27.806Z","profile":{"slug":"tirzepatide","name":"Tirzepatide","aliases":[],"category":"GIP/GLP-1 receptor agonist"},"synthesis":{"mechanism":"Tirzepatide is a long-acting peptide agonist at GIP and GLP-1 receptors. Controlled programs evaluate glycemic control, chronic weight management, withdrawal, obesity-related obstructive sleep apnea, HFpEF with obesity, and MASH. Regulatory conclusions remain indication- and label-specific.","evidence":"The governed corpus spans SURPASS diabetes trials, SURMOUNT obesity and withdrawal trials, active-comparator evidence, OSA, HFpEF with obesity, and phase 2 MASH evidence. Claims remain bounded by population, comparator, dose, duration, and endpoint.","safety":"Gastrointestinal adverse reactions are prominent and may lead to discontinuation. Current prescribing information controls contraindications and warnings, including thyroid C-cell tumor findings in rodents, pancreatitis, gallbladder disease, volume-depletion kidney injury, severe gastrointestinal reactions, hypoglycemia with insulin or secretagogues, and hypersensitivity.","observationalBoundary":"Approved-product reference profile organized by indication and trial program.","openQuestions":"Priority surveillance includes long-term cardiovascular and renal comparisons; discontinuation and regain; uncommon harms; lean mass, nutrition, pregnancy, pediatric and underrepresented-population evidence; and MASH outcomes beyond histology."},"completion":{"version":"wpf-profile-v1.0","complete":true,"checks":[{"key":"overview","passed":true,"actual":291,"required":100,"severity":"blocking"},{"key":"evidence_summary","passed":true,"actual":249,"required":100,"severity":"blocking"},{"key":"safety_summary","passed":true,"actual":374,"required":100,"severity":"blocking"},{"key":"archive_boundary","passed":true,"actual":77,"required":75,"severity":"blocking"},{"key":"open_questions","passed":true,"actual":243,"required":75,"severity":"blocking"},{"key":"verified_sources","passed":true,"actual":25,"required":25,"severity":"blocking"},{"key":"reviewed_sources","passed":true,"actual":25,"required":1,"severity":"blocking"},{"key":"chemistry","passed":true,"actual":true,"required":true,"severity":"blocking"},{"key":"regulatory_context","passed":true,"actual":2,"required":2,"severity":"blocking"},{"key":"claims","passed":true,"actual":25,"required":1,"severity":"blocking"},{"key":"claim_traceability","passed":true,"actual":0,"required":0,"severity":"blocking"},{"key":"regulatory_freshness","passed":true,"actual":0,"required":0,"severity":"warning"}],"failures":[]},"chemistry":{"id":"02f03295fb175a8310f537e53a1d68e1","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","molecularFormula":"C225H348N48O68","molecularWeight":4813.45,"aminoAcidSequence":null,"smiles":null,"inchi":null,"inchikey":"BTSOGEDATSQOAF-MCNPHUAVSA-N","structureImageUrl":"https://pubchem.ncbi.nlm.nih.gov/compound/156588324","createdAt":"2026-09-08T19:54:15.803Z","updatedAt":"2026-09-08T19:54:15.803Z"},"evidence":[{"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":"892ec5770f3d0482a36a700a902ff5cb","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Semaglutide and tirzepatide effects on cardiovascular outcomes in people with overweight or obesity in the real world (STEER).","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/41491349/","evidenceTier":"observational","summary":"To assess the real-world effectiveness of semaglutide versus tirzepatide in reducing major adverse cardiovascular events (MACE) among patients with overweight/obesity and established atherosclerotic cardiovascular disease (ASCVD) without diabetes in an insured US population. This retrospective, observational cohort study used Komodo Research Data and included patients ≥45 years of age with overweight/obesity and ≥1 claim for myocardial infarction (MI), ischemic stroke, or peripheral artery disease first treated with semaglutide or tirzepatide between 13/5/2022-31/1/2025. Propensity score matching was used to balance key baseline characteristics between cohorts. 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":"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":"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":"38dae3dd050ab0d48c95f54431ea0fd5","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Efficacy and safety of tirzepatide in children and adolescents with type 2 diabetes (SURPASS-PEDS): a randomised, double-blind, placebo-controlled, phase 3 trial.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/40975112/","evidenceTier":"phase_3","summary":"Current treatment options for youth-onset type 2 diabetes are limited and have demonstrated lower glycaemic efficacy than those for adult-onset type 2 diabetes. We aimed to assess the safety and efficacy of tirzepatide, a glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist, compared with placebo in youth-onset type 2 diabetes. We conducted a phase 3, double-blind, placebo-controlled, multicentre (39 sites), multinational (eight countries) trial over 30 weeks, followed by an open-label extension for 22 weeks in which all participants received tirzepatide. Participants aged 10 to <18 years with youth-onset type 2 diabetes inadequately controlled with metformin and/or...","authors":"Tamara S Hannon, Lily C Chao, Margarita Barrientos-Pérez, Karthik Chandrasekhar Pamidipati, Laura Fernández Landó, Clare J Lee, Hiren Patel, Brandon K Bergman","publishingOrg":null,"publicationYear":2025,"doi":"10.1016/S0140-6736(25)01774-X","pubmedId":"40975112","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 tirzepatide in children and adolescents with type 2 diabetes (SURPASS-PEDS): a randomised, double-blind, placebo-controlled, 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(25)01774-x","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","Clinical Trial, Phase III","Randomized Controlled Trial","Multicenter Study"]},"provenancePayload":{"doi":"10.1016/S0140-6736(25)01774-X","pmid":"40975112","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":"ca3e3780-3b8b-47f9-b94e-5a1ce07dcdd2","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/39555826/","evidenceTier":"phase_3","summary":"In 731 adults with HFpEF and obesity, tirzepatide reduced cardiovascular death or worsening heart-failure events and improved health status versus placebo.","authors":null,"publishingOrg":null,"publicationYear":2025,"doi":"10.1056/NEJMoa2410027","pubmedId":"39555826","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/NEJMoa2410027","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 event-driven phase 3 trial.","limitations":["The phenotype-specific population, event count, follow-up, and sponsor involvement affect generalization."],"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/NEJMoa2410027","pmid":"39555826"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T17:59:47.986Z","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":"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":"75a043de-2df7-4730-8fbd-c3bb7ace765e","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/38078870/","evidenceTier":"phase_3","summary":"After a tirzepatide lead-in, 670 participants were randomized; continued treatment maintained and extended loss, while withdrawal led to regain.","authors":null,"publishingOrg":null,"publicationYear":2024,"doi":"10.1001/jama.2023.24945","pubmedId":"38078870","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:10.1001/jama.2023.24945","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 withdrawal phase 3 trial.","limitations":["Run-in enrichment does not estimate initiation effects in people unable to tolerate therapy."],"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.2023.24945","pmid":"38078870"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T17:59:47.986Z","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":"4cdf420d-72e1-4cc9-bb92-31d8922e2778","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/38856224/","evidenceTier":"phase_1_2","summary":"In 190 adults with biopsy-confirmed MASH and F2/F3 fibrosis, tirzepatide increased histologic MASH resolution without worsening fibrosis at 52 weeks.","authors":null,"publishingOrg":null,"publicationYear":2024,"doi":"10.1056/NEJMoa2401943","pubmedId":"38856224","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/NEJMoa2401943","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 2 trial.","limitations":["Phase 2 sample, duration, and histologic surrogate endpoints constrain conclusions."],"sourceStrength":{"note":"Automated baseline based on evidence tier; full-text risk-of-bias review may revise it","grade":"B+","score":82,"version":"WPF-ESR-1.0","provisional":true}},"provenancePayload":{"doi":"10.1056/NEJMoa2401943","pmid":"38856224"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T17:59:47.986Z","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":"4ab1a8d7-b81c-4245-937b-59821adbde02","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/38912654/","evidenceTier":"phase_3","summary":"Two phase 3 trials in 469 adults with obesity and moderate-to-severe OSA found reductions in apnea-hypopnea index and weight versus placebo.","authors":null,"publishingOrg":null,"publicationYear":2024,"doi":"10.1056/NEJMoa2404881","pubmedId":"38912654","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/NEJMoa2404881","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":"Two randomized double-blind placebo-controlled phase 3 trials.","limitations":["PAP strata, phenotype, duration, and weight-mediated effects require context."],"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/NEJMoa2404881","pmid":"38912654"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T17:59:47.986Z","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":"ae9845f1-2c5e-44da-825d-b80f0c9a7263","peptideId":"03857218-503c-43b9-9971-39bca8a2ecde","title":"Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/37845521/","evidenceTier":"phase_3","summary":"After an intensive lifestyle lead-in, 579 adults were randomized and tirzepatide produced additional weight reduction versus placebo.","authors":null,"publishingOrg":null,"publicationYear":2023,"doi":"10.1038/s41591-023-02597-w","pubmedId":"37845521","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:10.1038/s41591-023-02597-w","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 after lifestyle lead-in.","limitations":["Lead-in enrichment means results do not represent every treatment initiator."],"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/s41591-023-02597-w","pmid":"37845521"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T17:59:47.986Z","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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