{"schemaVersion":"wpf-profile-export-v1","exportedAt":"2026-09-18T15:18:18.074Z","profile":{"slug":"semaglutide","name":"Semaglutide","aliases":[],"category":"GLP-1 receptor agonist"},"synthesis":{"mechanism":"Semaglutide is a long-acting analogue of human glucagon-like peptide-1 (GLP-1) engineered for resistance to DPP-4 degradation and prolonged albumin binding. It selectively activates the GLP-1 receptor. 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.","evidence":"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.","safety":"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.","observationalBoundary":"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.","openQuestions":"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."},"completion":{"version":"wpf-profile-v1.0","complete":true,"checks":[{"key":"overview","passed":true,"actual":621,"required":100,"severity":"blocking"},{"key":"evidence_summary","passed":true,"actual":865,"required":100,"severity":"blocking"},{"key":"safety_summary","passed":true,"actual":859,"required":100,"severity":"blocking"},{"key":"archive_boundary","passed":true,"actual":378,"required":75,"severity":"blocking"},{"key":"open_questions","passed":true,"actual":484,"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":"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"},"evidence":[{"id":"5cb9b49d-7c71-470a-9d3a-a678a0f6039f","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"WEGOVY (semaglutide) prescribing information, revised June 2026","sourceUrl":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215256s025lbl.pdf","evidenceTier":"fda_approved","summary":"The current US prescribing information defines approved indications, dosing, contraindications, warnings, adverse reactions, pharmacology, and clinical-study evidence for Wegovy. Label claims are jurisdiction-, formulation-, dose-, and revision-specific.","authors":null,"publishingOrg":null,"publicationYear":2026,"doi":null,"pubmedId":null,"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":"official_product_labeling","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":"url:https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215256s025lbl.pdf","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T17:41:50.436Z","retrievalProvider":"US FDA","retrievalPayloadRef":"wpf:semaglutide-reference-corpus:2026-09-08","evidenceLane":"regulatory","extractionPayload":{"finding":"The June 2026 FDA label is the controlling source for current US Wegovy indications, dosing, contraindications, warnings, and labeled evidence.","summary":"The current US prescribing information defines approved indications, dosing, contraindications, warnings, adverse reactions, pharmacology, and clinical-study evidence for Wegovy. Label claims are jurisdiction-, formulation-, dose-, and revision-specific.","population":"Patients and indications specified in the United States label","sampleSize":null,"limitations":["Regulatory labeling is jurisdiction- and revision-specific and does not substitute for individualized clinical judgment."],"studyDesign":"Official United States prescribing information","sourceStrength":{"note":"Automated baseline based on evidence tier; full-text risk-of-bias review may revise it","grade":"A+","score":95,"version":"WPF-ESR-1.0","provisional":true}},"provenancePayload":{"doi":null,"pmid":null,"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":"506d0e62b8591722452e80bd882c6414","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/40544433/","evidenceTier":"phase_3","summary":"A phase 3a multicenter double-blind trial evaluated coadministered cagrilintide and semaglutide versus active components and placebo for weight management in adults without diabetes.","authors":"W Timothy Garvey, Matthias Blüher, Cynthia Karenina Osorto Contreras, Melanie J Davies, Eva Winning Lehmann, Kirsi H Pietiläinen, Domenica Rubino, Paolo Sbraccia","publishingOrg":null,"publicationYear":2025,"doi":"10.1056/NEJMoa2502081","pubmedId":"40544433","jurisdiction":null,"dateAccessed":"2026-09-08T18:49:31.510Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity.","supportNature":"contextualizes","qualification":"Combination-therapy evidence cannot be attributed to semaglutide alone; applicability is limited to the studied regimen and population.","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/nejmoa2502081","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:49:31.510Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:semaglutide:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Combination-therapy evidence cannot be attributed to semaglutide alone; applicability is limited to the studied regimen and population."],"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":3,"designAndBias":40,"populationRelevance":15},"provisional":true}},"provenancePayload":{"doi":"10.1056/NEJMoa2502081","pmid":"40544433","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:49:31.510Z","updatedAt":"2026-09-08T18:49:31.510Z"},{"id":"09611e2fbd08f544363a797ac3cf7b0a","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/39937469/","evidenceTier":"phase_1_2","summary":"A small phase 2 double-blind randomized trial evaluated once-weekly semaglutide for alcohol consumption and craving in adults with alcohol use disorder.","authors":"Christian S Hendershot, Michael P Bremmer, Michael B Paladino, Georgios Kostantinis, Thomas A Gilmore, Neil R Sullivan, Amanda C Tow, Sarah S Dermody","publishingOrg":null,"publicationYear":2025,"doi":"10.1001/jamapsychiatry.2024.4789","pubmedId":"39937469","jurisdiction":null,"dateAccessed":"2026-09-08T18:49:31.510Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A 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/jamapsychiatry.2024.4789","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:49:31.510Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:semaglutide: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":3,"designAndBias":35,"populationRelevance":15},"provisional":true}},"provenancePayload":{"doi":"10.1001/jamapsychiatry.2024.4789","pmid":"39937469","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:49:31.510Z","updatedAt":"2026-09-08T18:49:31.510Z"},{"id":"5ade22f345927c5854fdfaffee42b17b","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/40961952/","evidenceTier":"phase_3","summary":"STEP UP was a phase 3b randomized, double-blind, placebo- and active-controlled trial comparing semaglutide 7.2 mg, 2.4 mg, and placebo in adults with obesity without diabetes.","authors":"Sean Wharton, Paula Freitas, Jøran Hjelmesæth, Maria Kabisch, Kristian Kandler, Ildiko Lingvay, Maria Quiroga, Julio Rosenstock","publishingOrg":null,"publicationYear":2025,"doi":"10.1016/S2213-8587(25)00226-8","pubmedId":"40961952","jurisdiction":null,"dateAccessed":"2026-09-08T18:49:31.510Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b 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)00226-8","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:49:31.510Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:semaglutide: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":3,"designAndBias":40,"populationRelevance":15},"provisional":true}},"provenancePayload":{"doi":"10.1016/S2213-8587(25)00226-8","pmid":"40961952","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:49:31.510Z","updatedAt":"2026-09-08T18:49:31.510Z"},{"id":"52202c7e51446e0b3fd46d4144cf9239","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/40162642/","evidenceTier":"phase_1_2","summary":"A double-blind event-driven superiority trial evaluated oral semaglutide in people with type 2 diabetes and atherosclerotic cardiovascular disease, chronic kidney disease, or both.","authors":"Darren K McGuire, Nikolaus Marx, Sharon L Mulvagh, John E Deanfield, Silvio E Inzucchi, Rodica Pop-Busui, Johannes F E Mann, Scott S Emerson","publishingOrg":null,"publicationYear":2025,"doi":"10.1056/NEJMoa2501006","pubmedId":"40162642","jurisdiction":null,"dateAccessed":"2026-09-08T18:49:31.510Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes.","supportNature":"contextualizes","qualification":"Applicability is limited to the enrolled high-risk population, oral formulation, 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/nejmoa2501006","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:49:31.510Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:semaglutide:expansion:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Applicability is limited to the enrolled high-risk population, oral formulation, 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":3,"designAndBias":35,"populationRelevance":15},"provisional":true}},"provenancePayload":{"doi":"10.1056/NEJMoa2501006","pmid":"40162642","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:49:31.510Z","updatedAt":"2026-09-08T18:49:31.510Z"},{"id":"3d0f49fe-cf2a-440a-a2ef-e54f12474817","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/40353578/","evidenceTier":"phase_3","summary":"In a 72-week, phase 3b randomized open-label trial of 751 adults with obesity without type 2 diabetes, mean body-weight change was −13.7% with semaglutide and −20.2% with tirzepatide. Gastrointestinal adverse events were the most common adverse events in both groups. Interpretation is limited to the studied population, doses, duration, active comparator, and open-label design.","authors":null,"publishingOrg":null,"publicationYear":2025,"doi":"10.1056/NEJMoa2416394","pubmedId":"40353578","jurisdiction":null,"dateAccessed":"2026-09-08T17:21:53.433Z","editorialNotes":"AI-assisted scientific review; Owner-authorized publication 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-flagship-semglp1-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1056/NEJMoa2416394","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T17:21:53.433Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"repo:aiReviewFirst10.json","evidenceLane":"human_interventional","extractionPayload":{"summary":"In a 72-week, phase 3b randomized open-label trial of 751 adults with obesity without type 2 diabetes, mean body-weight change was −13.7% with semaglutide and −20.2% with tirzepatide. Gastrointestinal adverse events were the most common adverse events in both groups. Interpretation is limited to the studied population, doses, duration, active comparator, and open-label design.","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/NEJMoa2416394","pmid":"40353578","reviewAsset":"aiReviewFirst10.json"},"validationGates":{"doiResolved":true,"pmidResolved":true,"ownerAuthorized":true,"identityResolved":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T17:21:53.433Z","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":"48a871dc50f45177152378efe6106b76","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Patients Without Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/38679221/","evidenceTier":"observational","summary":"Systematic review and meta-analysis of randomized trials examining long-term efficacy and safety of once-weekly semaglutide for weight loss in adults without diabetes.","authors":"Areesha Moiz, Jeremy Y Levett, Kristian B Filion, Katya Peri, Pauline Reynier, Mark J Eisenberg","publishingOrg":null,"publicationYear":2024,"doi":"10.1016/j.amjcard.2024.04.041","pubmedId":"38679221","jurisdiction":null,"dateAccessed":"2026-09-08T18:49:31.510Z","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 Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Patients Without Diabetes: 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.amjcard.2024.04.041","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:49:31.510Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:semaglutide: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":5,"designAndBias":32,"populationRelevance":11},"provisional":true}},"provenancePayload":{"doi":"10.1016/j.amjcard.2024.04.041","pmid":"38679221","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:49:31.510Z","updatedAt":"2026-09-08T18:49:31.510Z"},{"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. Participants with obesity and knee osteoarthritis were randomized to semaglutide or placebo.","authors":"Henning Bliddal, Harold Bays, Sébastien Czernichow, Joanna Uddén Hemmingsson, Jøran Hjelmesæth, Thomas Hoffmann Morville, Anna Koroleva, Jesper Skov Neergaard","publishingOrg":null,"publicationYear":2024,"doi":"10.1056/NEJMoa2403664","pubmedId":"39476339","jurisdiction":null,"dateAccessed":"2026-09-08T18:49:31.510Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis.","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/nejmoa2403664","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:49:31.510Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:semaglutide: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":3,"designAndBias":40,"populationRelevance":15},"provisional":true}},"provenancePayload":{"doi":"10.1056/NEJMoa2403664","pmid":"39476339","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:49:31.510Z","updatedAt":"2026-09-08T18:49:31.510Z"},{"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. Oral semaglutide produced substantially greater weight reduction, with gastrointestinal adverse events more frequent during treatment.","authors":null,"publishingOrg":null,"publicationYear":2023,"doi":"10.1016/S0140-6736(23)01185-6","pubmedId":"37385278","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/S0140-6736(23)01185-6","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":"Once-daily oral semaglutide 50 mg produced greater weight reduction than placebo at 68 weeks in the studied population.","summary":"OASIS 1 randomized 667 adults without type 2 diabetes to once-daily oral semaglutide 50 mg or placebo for 68 weeks. Oral semaglutide produced substantially greater weight reduction, with gastrointestinal adverse events more frequent during treatment.","population":"Adults with overweight or obesity without type 2 diabetes","sampleSize":"667","limitations":["The 50 mg oral regimen, selected population, treatment duration, sponsor involvement, and gastrointestinal tolerability constrain interpretation."],"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":"10.1016/S0140-6736(23)01185-6","pmid":"37385278","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":"aa426afc-84ee-4eef-84fa-dfd59183c8b1","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/35015037/","evidenceTier":"phase_3","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.","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":"de07c02e-4670-4962-8fee-7aaa962df882","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Efficacy and Safety of Semaglutide for Weight Loss in Obesity Without Diabetes: A Systematic Review and Meta-Analysis.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/36578889/","evidenceTier":"phase_3","summary":"A random-effects meta-analysis of four randomized trials comprising 3,613 participants with obesity without diabetes found greater weight reduction with subcutaneous semaglutide than placebo and higher risks of gastrointestinal adverse events and treatment discontinuation. Conclusions inherit the designs, populations, durations, and quality of the included trials.","authors":null,"publishingOrg":null,"publicationYear":2022,"doi":"10.15605/jafes.037.02.14","pubmedId":"36578889","jurisdiction":null,"dateAccessed":"2026-09-08T17:21:53.433Z","editorialNotes":"AI-assisted scientific review; Owner-authorized publication 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-flagship-semglp1-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.15605/jafes.037.02.14","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T17:21:53.433Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"repo:aiReviewFirst10.json","evidenceLane":"meta_analysis","extractionPayload":{"summary":"A random-effects meta-analysis of four randomized trials comprising 3,613 participants with obesity without diabetes found greater weight reduction with subcutaneous semaglutide than placebo and higher risks of gastrointestinal adverse events and treatment discontinuation. Conclusions inherit the designs, populations, durations, and quality of the included trials.","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":"10.15605/jafes.037.02.14","pmid":"36578889","reviewAsset":"aiReviewFirst10.json"},"validationGates":{"doiResolved":true,"pmidResolved":true,"ownerAuthorized":true,"identityResolved":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T17:21:53.433Z","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":"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. Semaglutide 2.4 mg produced greater weight reduction than placebo at 68 weeks, with gastrointestinal disorders the most frequent adverse events.","population":"Adults in East Asia with overweight or obesity, with or without type 2 diabetes","sampleSize":"401","limitations":["Regional eligibility, sample size, diabetes subgroup composition, and 68-week duration constrain generalization."],"studyDesign":"Randomized double-blind double-dummy 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":"10.1016/S2213-8587(22)00008-0","pmid":"35131037","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":"97a06214-0f56-4a3f-82dc-14be589edf0f","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/36216945/","evidenceTier":"phase_3","summary":"STEP 5 randomized 304 adults without diabetes to semaglutide 2.4 mg or placebo for 104 weeks. Semaglutide produced substantially greater sustained weight reduction; gastrointestinal disorders were the most frequent adverse events.","authors":null,"publishingOrg":null,"publicationYear":2022,"doi":"10.1038/s41591-022-02026-4","pubmedId":"36216945","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:10.1038/s41591-022-02026-4","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":"Weight loss with semaglutide was sustained over 104 weeks in the studied population and exceeded placebo.","summary":"STEP 5 randomized 304 adults without diabetes to semaglutide 2.4 mg or placebo for 104 weeks. 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":"9867aede-9a9d-4a53-915a-e2a1e2f8d144","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/35441470/","evidenceTier":"phase_3","summary":"This exploratory off-treatment extension followed 327 STEP 1 participants after withdrawal. Participants previously receiving semaglutide regained 11.6 percentage points of lost weight by week 120, and cardiometabolic measures generally moved toward baseline. The extension involved a subset of the parent trial and assessed withdrawal rather than continued randomized treatment.","authors":null,"publishingOrg":null,"publicationYear":2022,"doi":"10.1111/dom.14725","pubmedId":"35441470","jurisdiction":null,"dateAccessed":"2026-09-08T17:21:53.433Z","editorialNotes":"AI-assisted scientific review; Owner-authorized publication 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-flagship-semglp1-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1111/dom.14725","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T17:21:53.433Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"repo:aiReviewFirst10.json","evidenceLane":"human_observational","extractionPayload":{"summary":"This exploratory off-treatment extension followed 327 STEP 1 participants after withdrawal. Participants previously receiving semaglutide regained 11.6 percentage points of lost weight by week 120, and cardiometabolic measures generally moved toward baseline. The extension involved a subset of the parent trial and assessed withdrawal rather than continued randomized treatment.","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":"10.1111/dom.14725","pmid":"35441470","reviewAsset":"aiReviewFirst10.json"},"validationGates":{"doiResolved":true,"pmidResolved":true,"ownerAuthorized":true,"identityResolved":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T17:21:53.433Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"0c53eb01-7e83-445a-8567-baa0f0f554f0","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/33755728/","evidenceTier":"phase_3","summary":"After a 20-week semaglutide run-in, 803 adults were randomized to continue semaglutide 2.4 mg or switch to placebo for 48 weeks. Continued treatment led to further weight loss while switching to placebo led to weight regain.","authors":null,"publishingOrg":null,"publicationYear":2021,"doi":"10.1001/jama.2021.3224","pubmedId":"33755728","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.2021.3224","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":"Among run-in completers, continued semaglutide maintained and extended weight loss whereas withdrawal to placebo was followed by regain.","summary":"After a 20-week semaglutide run-in, 803 adults were randomized to continue semaglutide 2.4 mg or switch to placebo for 48 weeks. Continued treatment led to further weight loss while switching to placebo led to weight regain.","population":"Adults with overweight or obesity who tolerated and completed a 20-week semaglutide run-in","sampleSize":"803","limitations":["Enriched randomized population included only run-in completers who tolerated treatment; withdrawal design does not estimate initiation effects in an unselected population."],"studyDesign":"Randomized double-blind withdrawal 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":"10.1001/jama.2021.3224","pmid":"33755728","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":"544823d3-0802-4815-b939-bfca734b5cb4","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/33625476/","evidenceTier":"phase_3","summary":"In STEP 3, 611 adults without diabetes received intensive behavioral therapy and an initial low-calorie diet plus semaglutide 2.4 mg or placebo. At week 68, estimated mean weight change was -16.0% versus -5.7%; gastrointestinal events were more frequent with semaglutide.","authors":null,"publishingOrg":null,"publicationYear":2021,"doi":"10.1001/jama.2021.1831","pubmedId":"33625476","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.2021.1831","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":"At 68 weeks, semaglutide plus intensive behavioral therapy produced greater mean weight reduction than placebo plus the same intervention; gastrointestinal adverse events were more frequent.","summary":"In STEP 3, 611 adults without diabetes received intensive behavioral therapy and an initial low-calorie diet plus semaglutide 2.4 mg or placebo. At week 68, estimated mean weight change was -16.0% versus -5.7%; gastrointestinal events were more frequent with semaglutide.","population":"Adults with overweight or obesity without diabetes","sampleSize":"611","limitations":["Controlled duration was 68 weeks; both groups received intensive behavioral therapy and an initial low-calorie diet; sponsor involvement and studied eligibility criteria limit generalization."],"studyDesign":"Randomized double-blind phase 3a placebo-controlled 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":"10.1001/jama.2021.1831","pmid":"33625476","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":"6b679126-6947-4cc6-b541-0b2300cce650","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Once-Weekly Semaglutide in Adults with Overweight or Obesity.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/33567185/","evidenceTier":"phase_3","summary":"In STEP 1, 1,961 adults with overweight or obesity without diabetes were randomized to semaglutide 2.4 mg or placebo plus lifestyle intervention. At 68 weeks, mean body-weight change was −14.9% with semaglutide versus −2.4% with placebo; gastrointestinal adverse events and discontinuations for gastrointestinal events were more frequent with semaglutide. Results are limited to the studied population and duration.","authors":null,"publishingOrg":null,"publicationYear":2021,"doi":"10.1056/NEJMoa2032183","pubmedId":"33567185","jurisdiction":null,"dateAccessed":"2026-09-08T17:21:53.433Z","editorialNotes":"AI-assisted scientific review; Owner-authorized publication 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-flagship-semglp1-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1056/NEJMoa2032183","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T17:21:53.433Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"repo:aiReviewFirst10.json","evidenceLane":"human_interventional","extractionPayload":{"summary":"In STEP 1, 1,961 adults with overweight or obesity without diabetes were randomized to semaglutide 2.4 mg or placebo plus lifestyle intervention. At 68 weeks, mean body-weight change was −14.9% with semaglutide versus −2.4% with placebo; gastrointestinal adverse events and discontinuations for gastrointestinal events were more frequent with semaglutide. Results are limited to the studied population and duration.","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/NEJMoa2032183","pmid":"33567185","reviewAsset":"aiReviewFirst10.json"},"validationGates":{"doiResolved":true,"pmidResolved":true,"ownerAuthorized":true,"identityResolved":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T17:21:53.433Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"304125cd-eb9e-402e-9984-a5680792bcbc","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/33667417/","evidenceTier":"phase_3","summary":"In STEP 2, 1,210 adults with overweight or obesity and type 2 diabetes were randomized to semaglutide 2.4 mg, semaglutide 1.0 mg, or placebo. At 68 weeks, mean body-weight change was −9.6% with 2.4 mg versus −3.4% with placebo; gastrointestinal adverse events were more frequent with semaglutide. Results are specific to the studied population and duration.","authors":null,"publishingOrg":null,"publicationYear":2021,"doi":"10.1016/S0140-6736(21)00213-0","pubmedId":"33667417","jurisdiction":null,"dateAccessed":"2026-09-08T17:21:53.433Z","editorialNotes":"AI-assisted scientific review; Owner-authorized publication 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-flagship-semglp1-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/S0140-6736(21)00213-0","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T17:21:53.433Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"repo:aiReviewFirst10.json","evidenceLane":"human_interventional","extractionPayload":{"summary":"In STEP 2, 1,210 adults with overweight or obesity and type 2 diabetes were randomized to semaglutide 2.4 mg, semaglutide 1.0 mg, or placebo. At 68 weeks, mean body-weight change was −9.6% with 2.4 mg versus −3.4% with placebo; gastrointestinal adverse events were more frequent with semaglutide. Results are specific to the studied population and duration.","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/S0140-6736(21)00213-0","pmid":"33667417","reviewAsset":"aiReviewFirst10.json"},"validationGates":{"doiResolved":true,"pmidResolved":true,"ownerAuthorized":true,"identityResolved":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T17:21:53.433Z","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":"a9bbd4d4-d998-43ce-9627-5e0b95fd4e50","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"The Discovery and Development of Liraglutide and Semaglutide.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/31031702/","evidenceTier":"phase_1_2","summary":"This narrative review describes semaglutide molecular design, albumin-binding protraction, GLP-1 receptor pharmacology, and clinical development. It is useful for background and mechanism context but is not a primary efficacy estimate.","authors":null,"publishingOrg":null,"publicationYear":2019,"doi":"10.3389/fendo.2019.00155","pubmedId":"31031702","jurisdiction":null,"dateAccessed":"2026-09-08T17:21:53.433Z","editorialNotes":"AI-assisted scientific review; Owner-authorized publication 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-flagship-semglp1-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.3389/fendo.2019.00155","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T17:21:53.433Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"repo:aiReviewFirst10.json","evidenceLane":"mechanistic","extractionPayload":{"summary":"This narrative review describes semaglutide molecular design, albumin-binding protraction, GLP-1 receptor pharmacology, and clinical development. It is useful for background and mechanism context but is not a primary efficacy estimate.","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":"10.3389/fendo.2019.00155","pmid":"31031702","reviewAsset":"aiReviewFirst10.json"},"validationGates":{"doiResolved":true,"pmidResolved":true,"ownerAuthorized":true,"identityResolved":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T17:21:53.433Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"ba91a89b-4dcf-4215-8392-6fc02c882891","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","title":"Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/27633186/","evidenceTier":"phase_3","summary":"SUSTAIN-6 randomized 3,297 patients with type 2 diabetes to weekly semaglutide or placebo for 104 weeks. The primary cardiovascular outcome occurred in 6.6% versus 8.9% (hazard ratio 0.74). Retinopathy complications were more frequent with semaglutide, while new or worsening nephropathy was less frequent.","authors":null,"publishingOrg":null,"publicationYear":2016,"doi":"10.1056/NEJMoa1607141","pubmedId":"27633186","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/NEJMoa1607141","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 met cardiovascular noninferiority and the observed primary composite rate was lower than placebo; the trial also identified a higher retinopathy-complication rate.","summary":"SUSTAIN-6 randomized 3,297 patients with type 2 diabetes to weekly semaglutide or placebo for 104 weeks. The primary cardiovascular outcome occurred in 6.6% versus 8.9% (hazard ratio 0.74). Retinopathy complications were more frequent with semaglutide, while new or worsening nephropathy was less frequent.","population":"Patients with type 2 diabetes at high cardiovascular risk","sampleSize":"3297","limitations":["The trial was designed primarily for noninferiority, had 104-week duration, enrolled a high-risk population, and the retinopathy signal requires clinical context."],"studyDesign":"Randomized double-blind placebo-controlled cardiovascular 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/NEJMoa1607141","pmid":"27633186","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"}],"regulatory":[{"id":"8e9fce614ab87ad9922c9988da6d19bc","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","jurisdiction":"European Union (EMA)","status":"approved","approvedIndication":"Semaglutide is centrally authorised in the European Union in product-specific forms: Ozempic and Rybelsus for defined type 2 diabetes populations, and Wegovy for weight management in defined adults and adolescents. The applicable population, formulation, dose, contraindications, and current product information remain controlling.","rationale":"EU authorization is medicine-, formulation-, population-, and indication-specific. Approval of one semaglutide product does not transfer automatically to another formulation or use.","sourceTitle":"EMA EPARs — Wegovy, Ozempic and Rybelsus","sourceUrl":"https://www.ema.europa.eu/en/medicines/human/EPAR/wegovy","dateChecked":"2026-09-08T20:03:10.550Z","reviewDueAt":"2026-12-07T20:03:10.550Z","enteredById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","publicationStatus":"published","factualObservationId":null,"createdAt":"2026-09-08T20:03:10.550Z","updatedAt":"2026-09-08T20:03:10.550Z"},{"id":"ad04bcd4-29ac-4bba-8460-0dcd737b68b4","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","jurisdiction":"United States (FDA)","status":"approved","approvedIndication":"Current FDA labeling for Wegovy identifies semaglutide formulations for defined cardiovascular-risk reduction and chronic weight-reduction populations; Wegovy injection is also approved for defined adults with noncirrhotic MASH and moderate-to-advanced fibrosis under accelerated approval. Product, formulation, age, comorbidity, and indication restrictions apply.","rationale":"Regulatory status is product- and indication-specific. This entry records the current Wegovy label and does not imply that every semaglutide formulation is approved for every listed use.","sourceTitle":"FDA Wegovy Prescribing Information, revised June 2026","sourceUrl":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215256s025lbl.pdf","dateChecked":"2026-09-08T17:21:53.433Z","reviewDueAt":"2026-12-07T17:21:53.433Z","enteredById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","publicationStatus":"published","factualObservationId":null,"createdAt":"2026-09-08T17:21:53.433Z","updatedAt":"2026-09-08T17:21:53.433Z"}],"claims":[{"id":"86250cde-bd33-4939-a970-58360b14ca74","claimKey":"semaglutide:10.1016/s0140-6736(21)00213-0","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"In STEP 2, 1,210 adults with overweight or obesity and type 2 diabetes were randomized to semaglutide 2.4 mg, semaglutide 1.0 mg, or placebo. At 68 weeks, mean body-weight change was −9.6% with 2.4 mg versus −3.4% with placebo; gastrointestinal adverse events were more frequent with semaglutide. Results are specific to the studied population and duration.","scope":{"scope":"study-specific","sourceDoi":"10.1016/S0140-6736(21)00213-0","notMedicalAdvice":true},"createdAt":"2026-09-08T17:24:20.829Z","updatedAt":"2026-09-08T17:24:20.829Z","evidenceLinks":[{"id":"bb3fac24-f0bc-4f74-b184-15eb4d895e3d","claimId":"86250cde-bd33-4939-a970-58360b14ca74","evidenceId":"304125cd-eb9e-402e-9984-a5680792bcbc","relation":"supports","sourceExcerpt":null,"sourceLocator":"https://pubmed.ncbi.nlm.nih.gov/33667417/","createdAt":"2026-09-08T17:24:20.829Z"}]},{"id":"2f03560c-4358-427a-80eb-d4656dd9c018","claimKey":"semaglutide:10.1056/nejmoa2032183","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"In STEP 1, 1,961 adults with overweight or obesity without diabetes were randomized to semaglutide 2.4 mg or placebo plus lifestyle intervention. At 68 weeks, mean body-weight change was −14.9% with semaglutide versus −2.4% with placebo; gastrointestinal adverse events and discontinuations for gastrointestinal events were more frequent with semaglutide. Results are limited to the studied population and duration.","scope":{"scope":"study-specific","sourceDoi":"10.1056/NEJMoa2032183","notMedicalAdvice":true},"createdAt":"2026-09-08T17:24:20.829Z","updatedAt":"2026-09-08T17:24:20.829Z","evidenceLinks":[{"id":"fedbb9f6-bb1a-49d3-92c1-294ad45e9dde","claimId":"2f03560c-4358-427a-80eb-d4656dd9c018","evidenceId":"6b679126-6947-4cc6-b541-0b2300cce650","relation":"supports","sourceExcerpt":null,"sourceLocator":"https://pubmed.ncbi.nlm.nih.gov/33567185/","createdAt":"2026-09-08T17:24:20.829Z"}]},{"id":"775e63cc-5d61-4816-9ac6-35a673e6a6b6","claimKey":"semaglutide:10.1056/nejmoa2416394","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"In a 72-week, phase 3b randomized open-label trial of 751 adults with obesity without type 2 diabetes, mean body-weight change was −13.7% with semaglutide and −20.2% with tirzepatide. Gastrointestinal adverse events were the most common adverse events in both groups. Interpretation is limited to the studied population, doses, duration, active comparator, and open-label design.","scope":{"scope":"study-specific","sourceDoi":"10.1056/NEJMoa2416394","notMedicalAdvice":true},"createdAt":"2026-09-08T17:24:20.829Z","updatedAt":"2026-09-08T17:24:20.829Z","evidenceLinks":[{"id":"793a533d-9f89-4021-9130-5faf910951c2","claimId":"775e63cc-5d61-4816-9ac6-35a673e6a6b6","evidenceId":"3d0f49fe-cf2a-440a-a2ef-e54f12474817","relation":"supports","sourceExcerpt":null,"sourceLocator":"https://pubmed.ncbi.nlm.nih.gov/40353578/","createdAt":"2026-09-08T17:24:20.829Z"}]},{"id":"ff538be9-a0ba-4a9e-bddf-9e1c33483568","claimKey":"semaglutide:10.1111/dom.14725","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"This exploratory off-treatment extension followed 327 STEP 1 participants after withdrawal. Participants previously receiving semaglutide regained 11.6 percentage points of lost weight by week 120, and cardiometabolic measures generally moved toward baseline. The extension involved a subset of the parent trial and assessed withdrawal rather than continued randomized treatment.","scope":{"scope":"study-specific","sourceDoi":"10.1111/dom.14725","notMedicalAdvice":true},"createdAt":"2026-09-08T17:24:20.829Z","updatedAt":"2026-09-08T17:24:20.829Z","evidenceLinks":[{"id":"f10c285c-61b3-469c-9cb4-2067235b90b3","claimId":"ff538be9-a0ba-4a9e-bddf-9e1c33483568","evidenceId":"9867aede-9a9d-4a53-915a-e2a1e2f8d144","relation":"supports","sourceExcerpt":null,"sourceLocator":"https://pubmed.ncbi.nlm.nih.gov/35441470/","createdAt":"2026-09-08T17:24:20.829Z"}]},{"id":"d082b74f-1d2d-4b91-a7af-fbaa1f22ecf4","claimKey":"semaglutide:10.15605/jafes.037.02.14","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"A random-effects meta-analysis of four randomized trials comprising 3,613 participants with obesity without diabetes found greater weight reduction with subcutaneous semaglutide than placebo and higher risks of gastrointestinal adverse events and treatment discontinuation. Conclusions inherit the designs, populations, durations, and quality of the included trials.","scope":{"scope":"study-specific","sourceDoi":"10.15605/jafes.037.02.14","notMedicalAdvice":true},"createdAt":"2026-09-08T17:24:20.829Z","updatedAt":"2026-09-08T17:24:20.829Z","evidenceLinks":[{"id":"9d9a9081-1cd0-4bed-96db-14aa9e7167cb","claimId":"d082b74f-1d2d-4b91-a7af-fbaa1f22ecf4","evidenceId":"de07c02e-4670-4962-8fee-7aaa962df882","relation":"supports","sourceExcerpt":null,"sourceLocator":"https://pubmed.ncbi.nlm.nih.gov/36578889/","createdAt":"2026-09-08T17:24:20.829Z"}]},{"id":"36a9a61c-9691-4e57-8a21-28d6db07d14e","claimKey":"semaglutide:10.3389/fendo.2019.00155","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"This narrative review describes semaglutide molecular design, albumin-binding protraction, GLP-1 receptor pharmacology, and clinical development. It is useful for background and mechanism context but is not a primary efficacy estimate.","scope":{"scope":"study-specific","sourceDoi":"10.3389/fendo.2019.00155","notMedicalAdvice":true},"createdAt":"2026-09-08T17:24:20.829Z","updatedAt":"2026-09-08T17:24:20.829Z","evidenceLinks":[{"id":"0326f200-ff0e-4e4d-8455-152981673bac","claimId":"36a9a61c-9691-4e57-8a21-28d6db07d14e","evidenceId":"a9bbd4d4-d998-43ce-9627-5e0b95fd4e50","relation":"supports","sourceExcerpt":null,"sourceLocator":"https://pubmed.ncbi.nlm.nih.gov/31031702/","createdAt":"2026-09-08T17:24:20.829Z"}]},{"id":"2db996a4-07f7-4dfe-881f-74352355ce39","claimKey":"semaglutide:step3","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"In STEP 3, 611 adults without diabetes received intensive behavioral therapy and an initial low-calorie diet plus semaglutide 2.4 mg or placebo. At week 68, estimated mean weight change was -16.0% versus -5.7%; gastrointestinal events were more frequent with semaglutide.","scope":{"scope":"study-specific","sourceDoi":"10.1001/jama.2021.1831","sourcePmid":"33625476","candidateKey":"step3","notMedicalAdvice":true},"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T17:41:50.436Z","evidenceLinks":[{"id":"3cb4cd62-7acd-401e-b565-d4c14fe50e03","claimId":"2db996a4-07f7-4dfe-881f-74352355ce39","evidenceId":"544823d3-0802-4815-b939-bfca734b5cb4","relation":"supports","sourceExcerpt":"At 68 weeks, semaglutide plus intensive behavioral therapy produced greater mean weight reduction than placebo plus the same intervention; gastrointestinal adverse events were more frequent.","sourceLocator":"PubMed abstract PMID 33625476","createdAt":"2026-09-08T17:41:50.436Z"}]},{"id":"f4d65285-5759-4dc9-8097-65af4fb34063","claimKey":"semaglutide:step4","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"After a 20-week semaglutide run-in, 803 adults were randomized to continue semaglutide 2.4 mg or switch to placebo for 48 weeks. Continued treatment led to further weight loss while switching to placebo led to weight regain.","scope":{"scope":"study-specific","sourceDoi":"10.1001/jama.2021.3224","sourcePmid":"33755728","candidateKey":"step4","notMedicalAdvice":true},"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T17:41:50.436Z","evidenceLinks":[{"id":"219fc278-c2df-4709-8664-2c7a761dbc3a","claimId":"f4d65285-5759-4dc9-8097-65af4fb34063","evidenceId":"0c53eb01-7e83-445a-8567-baa0f0f554f0","relation":"mixed","sourceExcerpt":"Among run-in completers, continued semaglutide maintained and extended weight loss whereas withdrawal to placebo was followed by regain.","sourceLocator":"PubMed abstract PMID 33755728","createdAt":"2026-09-08T17:41:50.436Z"}]},{"id":"e40bdc8b-4ffe-4a09-800c-3decde09315e","claimKey":"semaglutide:step5","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"STEP 5 randomized 304 adults without diabetes to semaglutide 2.4 mg or placebo for 104 weeks. Semaglutide produced substantially greater sustained weight reduction; gastrointestinal disorders were the most frequent adverse events.","scope":{"scope":"study-specific","sourceDoi":"10.1038/s41591-022-02026-4","sourcePmid":"36216945","candidateKey":"step5","notMedicalAdvice":true},"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T17:41:50.436Z","evidenceLinks":[{"id":"dcae422f-3dfc-41d1-8265-2a6ffde3c0aa","claimId":"e40bdc8b-4ffe-4a09-800c-3decde09315e","evidenceId":"97a06214-0f56-4a3f-82dc-14be589edf0f","relation":"supports","sourceExcerpt":"Weight loss with semaglutide was sustained over 104 weeks in the studied population and exceeded placebo.","sourceLocator":"PubMed abstract PMID 36216945","createdAt":"2026-09-08T17:41:50.436Z"}]},{"id":"ec29c759-725f-43dc-9c66-a875a396a527","claimKey":"semaglutide:step6","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"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.","scope":{"scope":"study-specific","sourceDoi":"10.1016/S2213-8587(22)00008-0","sourcePmid":"35131037","candidateKey":"step6","notMedicalAdvice":true},"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T17:41:50.436Z","evidenceLinks":[{"id":"af0d2117-3c6a-4da5-9260-bd722606c6d5","claimId":"ec29c759-725f-43dc-9c66-a875a396a527","evidenceId":"48a0dde7-5517-465c-9d06-836483ec4d37","relation":"supports","sourceExcerpt":"Semaglutide 2.4 mg reduced body weight more than placebo in the studied East Asian population.","sourceLocator":"PubMed abstract PMID 35131037","createdAt":"2026-09-08T17:41:50.436Z"}]},{"id":"66c4ea6b-1fb7-459b-857e-59cdac2d2a4a","claimKey":"semaglutide:step8","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"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.","scope":{"scope":"study-specific","sourceDoi":"10.1001/jama.2021.23619","sourcePmid":"35015037","candidateKey":"step8","notMedicalAdvice":true},"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T17:41:50.436Z","evidenceLinks":[{"id":"f562bcd1-8e21-417e-9a2c-124bfb09e574","claimId":"66c4ea6b-1fb7-459b-857e-59cdac2d2a4a","evidenceId":"aa426afc-84ee-4eef-84fa-dfd59183c8b1","relation":"supports","sourceExcerpt":"Weekly semaglutide produced greater weight reduction than daily liraglutide over 68 weeks in the studied population.","sourceLocator":"PubMed abstract PMID 35015037","createdAt":"2026-09-08T17:41:50.436Z"}]},{"id":"4317449f-4594-4183-8672-0918887447ee","claimKey":"semaglutide:step-teens","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"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.","scope":{"scope":"study-specific","sourceDoi":"10.1056/NEJMoa2208601","sourcePmid":"36322838","candidateKey":"step-teens","notMedicalAdvice":true},"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T17:41:50.436Z","evidenceLinks":[{"id":"96c2793b-bd77-4896-94ac-3504bce65a5e","claimId":"4317449f-4594-4183-8672-0918887447ee","evidenceId":"109d5f77-28c6-45a2-8531-1f1bad7e35ba","relation":"mixed","sourceExcerpt":"Semaglutide plus lifestyle intervention reduced BMI more than placebo plus lifestyle intervention at 68 weeks in enrolled adolescents.","sourceLocator":"PubMed abstract PMID 36322838","createdAt":"2026-09-08T17:41:50.436Z"}]},{"id":"12c07b5d-288c-4054-ae92-dce907f43802","claimKey":"semaglutide:select","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"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.","scope":{"scope":"study-specific","sourceDoi":"10.1056/NEJMoa2307563","sourcePmid":"37952131","candidateKey":"select","notMedicalAdvice":true},"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T17:41:50.436Z","evidenceLinks":[{"id":"20de2e1e-e024-458b-b121-5c0ca3f49c0b","claimId":"12c07b5d-288c-4054-ae92-dce907f43802","evidenceId":"8b85171b-59b3-48c4-8e7e-c20ffe1e5a8b","relation":"mixed","sourceExcerpt":"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.","sourceLocator":"PubMed abstract PMID 37952131","createdAt":"2026-09-08T17:41:50.436Z"}]},{"id":"acd6a5f9-ef90-48da-a0a0-49cf2dfb0274","claimKey":"semaglutide:sustain6","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"SUSTAIN-6 randomized 3,297 patients with type 2 diabetes to weekly semaglutide or placebo for 104 weeks. The primary cardiovascular outcome occurred in 6.6% versus 8.9% (hazard ratio 0.74). Retinopathy complications were more frequent with semaglutide, while new or worsening nephropathy was less frequent.","scope":{"scope":"study-specific","sourceDoi":"10.1056/NEJMoa1607141","sourcePmid":"27633186","candidateKey":"sustain6","notMedicalAdvice":true},"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T17:41:50.436Z","evidenceLinks":[{"id":"f9c745c3-dc2b-414b-a054-89bf1f2456a7","claimId":"acd6a5f9-ef90-48da-a0a0-49cf2dfb0274","evidenceId":"ba91a89b-4dcf-4215-8392-6fc02c882891","relation":"mixed","sourceExcerpt":"Semaglutide met cardiovascular noninferiority and the observed primary composite rate was lower than placebo; the trial also identified a higher retinopathy-complication rate.","sourceLocator":"PubMed abstract PMID 27633186","createdAt":"2026-09-08T17:41:50.436Z"}]},{"id":"917f5508-4d67-417b-9847-1767525eef7d","claimKey":"semaglutide:pioneer6","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"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.","scope":{"scope":"study-specific","sourceDoi":"10.1056/NEJMoa1901118","sourcePmid":"31185157","candidateKey":"pioneer6","notMedicalAdvice":true},"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T17:41:50.436Z","evidenceLinks":[{"id":"4e4b48a3-9acf-459f-a495-727d113a8b15","claimId":"917f5508-4d67-417b-9847-1767525eef7d","evidenceId":"d790dbb0-2827-41f3-9eba-9133f5945b9a","relation":"mixed","sourceExcerpt":"The cardiovascular risk profile of oral semaglutide was noninferior to placebo over a median 15.9 months.","sourceLocator":"PubMed abstract PMID 31185157","createdAt":"2026-09-08T17:41:50.436Z"}]},{"id":"b496f885-5786-4ab3-ad76-1d066292232c","claimKey":"semaglutide:sustain-forte","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"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.","scope":{"scope":"study-specific","sourceDoi":"10.1016/S2213-8587(21)00174-1","sourcePmid":"34293304","candidateKey":"sustain-forte","notMedicalAdvice":true},"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T17:41:50.436Z","evidenceLinks":[{"id":"2b1cd505-0ef5-4701-b2db-2c4418da181e","claimId":"b496f885-5786-4ab3-ad76-1d066292232c","evidenceId":"3763c4d7-1ebf-4bc8-be52-f4e15f4f2200","relation":"supports","sourceExcerpt":"Semaglutide 2.0 mg provided modest additional glycemic and weight effects versus 1.0 mg in the studied population.","sourceLocator":"PubMed abstract PMID 34293304","createdAt":"2026-09-08T17:41:50.436Z"}]},{"id":"752ee017-31c7-4ac7-ae2d-2966d22e57d7","claimKey":"semaglutide:flow","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"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.","scope":{"scope":"study-specific","sourceDoi":"10.1056/NEJMoa2403347","sourcePmid":"38785209","candidateKey":"flow","notMedicalAdvice":true},"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T17:41:50.436Z","evidenceLinks":[{"id":"0d307fc3-e9d8-4b3a-bcfb-0836e6b400da","claimId":"752ee017-31c7-4ac7-ae2d-2966d22e57d7","evidenceId":"af86c3e1-3fa5-48e1-97b2-b5017239c9d5","relation":"supports","sourceExcerpt":"Semaglutide reduced the risk of the prespecified major kidney-disease composite outcome versus placebo in the FLOW population.","sourceLocator":"PubMed abstract PMID 38785209","createdAt":"2026-09-08T17:41:50.436Z"}]},{"id":"06f73a76-e707-4bb8-a805-3a3435404e39","claimKey":"semaglutide:oasis1","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"OASIS 1 randomized 667 adults without type 2 diabetes to once-daily oral semaglutide 50 mg or placebo for 68 weeks. Oral semaglutide produced substantially greater weight reduction, with gastrointestinal adverse events more frequent during treatment.","scope":{"scope":"study-specific","sourceDoi":"10.1016/S0140-6736(23)01185-6","sourcePmid":"37385278","candidateKey":"oasis1","notMedicalAdvice":true},"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T17:41:50.436Z","evidenceLinks":[{"id":"03e664f9-ed4c-47a9-b093-8f60184bb623","claimId":"06f73a76-e707-4bb8-a805-3a3435404e39","evidenceId":"92d8b1ea-d437-4846-ae33-f27bd5ddfbd8","relation":"mixed","sourceExcerpt":"Once-daily oral semaglutide 50 mg produced greater weight reduction than placebo at 68 weeks in the studied population.","sourceLocator":"PubMed abstract PMID 37385278","createdAt":"2026-09-08T17:41:50.436Z"}]},{"id":"9dd80aac-d248-4aa8-b71b-4429144080b4","claimKey":"semaglutide:fda-wegovy-2026","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"The current US prescribing information defines approved indications, dosing, contraindications, warnings, adverse reactions, pharmacology, and clinical-study evidence for Wegovy. Label claims are jurisdiction-, formulation-, dose-, and revision-specific.","scope":{"scope":"study-specific","sourceDoi":null,"sourcePmid":null,"candidateKey":"fda-wegovy-2026","notMedicalAdvice":true},"createdAt":"2026-09-08T17:41:50.436Z","updatedAt":"2026-09-08T17:41:50.436Z","evidenceLinks":[{"id":"a5450808-b1f8-40ff-a058-91daedf3f380","claimId":"9dd80aac-d248-4aa8-b71b-4429144080b4","evidenceId":"5cb9b49d-7c71-470a-9d3a-a678a0f6039f","relation":"contextualizes","sourceExcerpt":"The June 2026 FDA label is the controlling source for current US Wegovy indications, dosing, contraindications, warnings, and labeled evidence.","sourceLocator":"FDA prescribing information revised June 2026","createdAt":"2026-09-08T17:41:50.436Z"}]},{"id":"8315dd9dbc72c394e606652e11da7d61","claimKey":"semaglutide:pubmed:39476339","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"This source contributes human_interventional evidence concerning Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis.","scope":{"evidenceLane":"human_interventional","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","sourceStrengthGrade":"A","sourceStrengthScore":91},"createdAt":"2026-09-08T18:49:31.510Z","updatedAt":"2026-09-08T18:49:31.510Z","evidenceLinks":[{"id":"8067d0ed53cb3a07202cec147f5b5935","claimId":"8315dd9dbc72c394e606652e11da7d61","evidenceId":"ae08fcf1395551a3b9401def356a2b41","relation":"contextualizes","sourceExcerpt":null,"sourceLocator":"PubMed PMID 39476339","createdAt":"2026-09-08T18:49:31.510Z"}]},{"id":"62e77bf00e5a6bbc87769dd012206cd7","claimKey":"semaglutide:pubmed:38679221","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"This source contributes meta_analysis evidence concerning Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Patients Without Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","scope":{"evidenceLane":"meta_analysis","qualification":"Secondary synthesis; certainty depends on included studies, heterogeneity, publication bias, and review methods.","sourceStrengthGrade":"A","sourceStrengthScore":83},"createdAt":"2026-09-08T18:49:31.510Z","updatedAt":"2026-09-08T18:49:31.510Z","evidenceLinks":[{"id":"476d681993b10cb7dc61388c5f725ae8","claimId":"62e77bf00e5a6bbc87769dd012206cd7","evidenceId":"48a871dc50f45177152378efe6106b76","relation":"contextualizes","sourceExcerpt":null,"sourceLocator":"PubMed PMID 38679221","createdAt":"2026-09-08T18:49:31.510Z"}]},{"id":"27cd27ed2f4893545b158e1145b804a9","claimKey":"semaglutide:pubmed:40961952","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"This source contributes human_interventional evidence concerning Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial.","scope":{"evidenceLane":"human_interventional","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","sourceStrengthGrade":"A","sourceStrengthScore":91},"createdAt":"2026-09-08T18:49:31.510Z","updatedAt":"2026-09-08T18:49:31.510Z","evidenceLinks":[{"id":"76f4be96d4f8a2b7e2341c61c494d76f","claimId":"27cd27ed2f4893545b158e1145b804a9","evidenceId":"5ade22f345927c5854fdfaffee42b17b","relation":"contextualizes","sourceExcerpt":null,"sourceLocator":"PubMed PMID 40961952","createdAt":"2026-09-08T18:49:31.510Z"}]},{"id":"afda1cf82a1886c95a6c6494086a00a2","claimKey":"semaglutide:pubmed:39937469","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"This source contributes human_interventional evidence concerning Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial.","scope":{"evidenceLane":"human_interventional","qualification":"Applicability is limited to the enrolled population, formulation, comparator, endpoints, and follow-up duration.","sourceStrengthGrade":"A","sourceStrengthScore":86},"createdAt":"2026-09-08T18:49:31.510Z","updatedAt":"2026-09-08T18:49:31.510Z","evidenceLinks":[{"id":"b23b4cf32ecbb7180112ca4fa9438261","claimId":"afda1cf82a1886c95a6c6494086a00a2","evidenceId":"09611e2fbd08f544363a797ac3cf7b0a","relation":"contextualizes","sourceExcerpt":null,"sourceLocator":"PubMed PMID 39937469","createdAt":"2026-09-08T18:49:31.510Z"}]},{"id":"aab3f465d734b3c3dd48e01247774cfb","claimKey":"semaglutide:pubmed:40544433","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"This source contributes human_interventional evidence concerning Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity.","scope":{"evidenceLane":"human_interventional","qualification":"Combination-therapy evidence cannot be attributed to semaglutide alone; applicability is limited to the studied regimen and population.","sourceStrengthGrade":"A","sourceStrengthScore":91},"createdAt":"2026-09-08T18:49:31.510Z","updatedAt":"2026-09-08T18:49:31.510Z","evidenceLinks":[{"id":"48da7ccadc0cc227b57974f5c9d8293d","claimId":"aab3f465d734b3c3dd48e01247774cfb","evidenceId":"506d0e62b8591722452e80bd882c6414","relation":"contextualizes","sourceExcerpt":null,"sourceLocator":"PubMed PMID 40544433","createdAt":"2026-09-08T18:49:31.510Z"}]},{"id":"6c36b977a4a31242015a823c9a91283b","claimKey":"semaglutide:pubmed:40162642","peptideId":"d8413984-163f-4dd7-be25-d1ec492ff769","claimText":"This source contributes human_interventional evidence concerning Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes.","scope":{"evidenceLane":"human_interventional","qualification":"Applicability is limited to the enrolled high-risk population, oral formulation, endpoints, and follow-up duration.","sourceStrengthGrade":"A","sourceStrengthScore":86},"createdAt":"2026-09-08T18:49:31.510Z","updatedAt":"2026-09-08T18:49:31.510Z","evidenceLinks":[{"id":"6bd56d041bfe79a354d8b85e53ee1f40","claimId":"6c36b977a4a31242015a823c9a91283b","evidenceId":"52202c7e51446e0b3fd46d4144cf9239","relation":"contextualizes","sourceExcerpt":null,"sourceLocator":"PubMed PMID 40162642","createdAt":"2026-09-08T18:49:31.510Z"}]}],"correctionHistory":[],"boundaries":{"observationsAreEvidence":false,"completionIsPublicationApproval":false,"medicalAdvice":false}}