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Evidence current through August 2026

Retatrutide

Retatrutide

LY3437943, the investigational molecule developed by Eli Lilly and commonly known as retatrutide, has become one of the most closely watched subjects in current metabolic research. It was designed to activate three hormone receptors studied in appetite, glucose, and energy-metabolism pathways: the glucose-dependent insulinotropic polypeptide receptor (GIPR), glucagon-like peptide-1 receptor (GLP-1R), and glucagon receptor (GCGR). This three-receptor design is why the molecule is commonly called a “triple agonist.”

In randomized human trials of Lilly’s investigated molecule, researchers reported unusually large changes in body-weight endpoints and meaningful changes in prespecified glycemic measures. Emerging datasets also reported signals involving liver fat, sleep-apnea endpoints, body composition, and knee-osteoarthritis symptoms. Together, these findings have made the triple-receptor strategy an important research question within the incretin field.

Evidence at a glance

What the current record supports

Qualification

Limitations and evidence gaps

Research path

Connected research articles

Overview

Retatrutide: Complete Research Overview

LY3437943, the investigational molecule developed by Eli Lilly and commonly known as retatrutide, has become one of the most closely watched subjects in current metabolic research. It was designed to activate three hormone receptors...
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Full review

Retatrutide Full Evidence Review

Retatrutide has a well-defined molecular and receptor-pharmacology record, substantial randomized evidence for weight and glycemic endpoints, and a large ongoing clinical program. Evidence strength differs sharply by question: the Phase 2 obesity and diabetes...
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Focused article

Body-Weight Findings in Retatrutide Trials

Trials of Lilly’s investigated LY3437943 have reported some of the largest mean body-weight changes in randomized metabolic research. These results are a major reason for scientific interest in the triple-agonist strategy, and understanding the...
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Study map

Connected study records

Identity, discovery, and analytical recordsSee approved evidence mapCompleted

Cell Metabolism

RET-STUDY-P002

Coskun T, et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist for glycemic control and weight loss. Cell Metabolism. 2022. DOI: 10.1016/j.cmet.2022.07.013. PMID: 35985340. NCT03841630. https://www.cell.com/cell-metabolism/

View study
Peer-reviewed human trials and related publicationsSee approved evidence mapCompleted

Lancet

RET-STUDY-P003

Urva S, et al. Retatrutide multiple-ascending-dose Phase 1b study in type 2 diabetes. Lancet. 2022. DOI: 10.1016/S0140-6736(22)02033-5. PMID: 36354040. NCT04143802. https://pubmed.ncbi.nlm.nih.gov/36354040/

View study
Peer-reviewed human trials and related publicationsSee approved evidence mapCompleted

New England Journal of Medicine

RET-STUDY-P004

Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity. New England Journal of Medicine. 2023. DOI: 10.1056/NEJMoa2301972. PMID: 37366315. NCT04881760. https://doi.org/10.1056/NEJMoa2301972

View study
Peer-reviewed human trials and related publicationsSee approved evidence mapCompleted

Lancet

RET-STUDY-P005

Rosenstock J, et al. Retatrutide in type 2 diabetes. Lancet. 2023. DOI: 10.1016/S0140-6736(23)01053-X. PMID: 37385280. NCT04867785. https://pubmed.ncbi.nlm.nih.gov/37385280/

View study
Peer-reviewed human trials and related publicationsSee approved evidence mapCompleted

Nature Medicine

RET-STUDY-P006

Sanyal AJ, et al. Retatrutide and liver fat in the Phase 2 obesity cohort. Nature Medicine. 2024. DOI: 10.1038/s41591-024-03018-2. PMID: 38858523. PMCID: PMC11271400. https://pmc.ncbi.nlm.nih.gov/articles/PMC11271400/

View study
Peer-reviewed human trials and related publicationsSee approved evidence mapCompleted

Lancet Diabetes & Endocrinology

RET-STUDY-P007

Coskun T, et al. Retatrutide body-composition substudy. Lancet Diabetes & Endocrinology. 2025. DOI: 10.1016/S2213-8587(25)00092-0. PMID: 40609566. https://pubmed.ncbi.nlm.nih.gov/40609566/

View study
Peer-reviewed human trials and related publicationsSee approved evidence mapCompleted

Lancet

RET-STUDY-P008

TRANSCEND-T2D-1 investigators. Phase 3 retatrutide in type 2 diabetes. Lancet. 2026. DOI: 10.1016/S0140-6736(26)00967-0. PMID: 42250575. NCT06354660. https://pubmed.ncbi.nlm.nih.gov/42250575/

View study
Peer-reviewed human trials and related publicationsSee approved evidence mapCompleted

Diabetes, Obesity and Metabolism

RET-STUDY-P009

Giblin K, et al. TRIUMPH-1 through TRIUMPH-4 design, estimands, and multiplicity. Diabetes, Obesity and Metabolism. 2026. DOI: 10.1111/dom.70209. PMID: 41090431. PMCID: PMC12673447. Design article; no results. https://pmc.ncbi.nlm.nih.gov/articl

View study
Conference, sponsor-topline, and registry recordsSee approved evidence mapOngoing

Retatrutide Clinical Trial Registry and Cross-Registry Audit

RET-STUDY-P014

ClinicalTrials.gov retatrutide study records and cross-registry audit. Registry evidence; result status varies by record. https://clinicaltrials.gov/api/v2/studies?query.term=AREA%5BInterventionName%5Dretatrutide%20OR%20AREA%5BInterventionName%5

View study
Peer-reviewed human trials and related publicationsSee approved evidence mapCompleted

Rationale, Design, and Baseline Characteristics of the TRANSCEND-CKD Trial of Retatrutide in Patients With Chronic Kidney Disease

RET-STUDY-P032

Heerspink HJL, van Raalte DH, Bjornstad P, et al. Rationale, design and baseline characteristics of the TRANSCEND-CKD trial of retatrutide in patients with chronic kidney disease. Nephrology Dialysis Transplantation. 2026;41(6):1058–1068. DOI: 10.1093/ndt/gfaf230. PMID: 41160422. PMCID: PMC13218929. NCT05936151. Design and baseline publication only. https://pmc.ncbi.nlm.nih.gov/articles/PMC13218929/

View study

Source ledger

References

  1. P001Identity, discovery, and analytical records

    PubChem CID 171390338; KEGG D12430; FDA GSRS UNII NOP2Y096GV; WHO INN List 128. Curated and regulatory identity records. https://pubchem.ncbi.nlm.nih.gov/compound/171390338

    PubChem CID 171390338; KEGG D12430; FDA GSRS UNII NOP2Y096GV; WHO INN List 128. Curated and regulatory identity records. https://pubchem.ncbi.nlm.nih.gov/compound/171390338

  2. P002Identity, discovery, and analytical records

    Cell Metabolism

    Coskun T, et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist for glycemic control and weight loss. Coskun T, et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist for glycemic control and weight loss. Cell Metabolism. 2022. DOI: 10.1016/j.cmet.2022.07.013. PMID: 35985340. NCT03841630. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00312-6(2022). DOI: 10.1016/j.cmet.2022.07.013

  3. P003Peer-reviewed human trials and related publications

    Lancet

    Urva S, et al. Retatrutide multiple-ascending-dose Phase 1b study in type 2 diabetes. Urva S, et al. Retatrutide multiple-ascending-dose Phase 1b study in type 2 diabetes. Lancet. 2022. DOI: 10.1016/S0140-6736(22)02033-5. PMID: 36354040. NCT04143802. https://pubmed.ncbi.nlm.nih.gov/36354040/(2022). DOI: 10.1016/S0140-6736(22

  4. P004Peer-reviewed human trials and related publications

    New England Journal of Medicine

    Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity. Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity. New England Journal of Medicine. 2023. DOI: 10.1056/NEJMoa2301972. PMID: 37366315. NCT04881760. https://doi.org/10.1056/NEJMoa2301972(2023). DOI: 10.1056/NEJMoa2301972

  5. P005Peer-reviewed human trials and related publications

    Lancet

    Rosenstock J, et al. Retatrutide in type 2 diabetes. Rosenstock J, et al. Retatrutide in type 2 diabetes. Lancet. 2023. DOI: 10.1016/S0140-6736(23)01053-X. PMID: 37385280. NCT04867785. https://pubmed.ncbi.nlm.nih.gov/37385280/(2023). DOI: 10.1016/S0140-6736(23

  6. P006Peer-reviewed human trials and related publications

    Nature Medicine

    Sanyal AJ, et al. Retatrutide and liver fat in the Phase 2 obesity cohort. Sanyal AJ, et al. Retatrutide and liver fat in the Phase 2 obesity cohort. Nature Medicine. 2024. DOI: 10.1038/s41591-024-03018-2. PMID: 38858523. PMCID: PMC11271400. https://pmc.ncbi.nlm.nih.gov/articles/PMC11271400/(2024). DOI: 10.1038/s41591-024-03018-2

  7. P007Peer-reviewed human trials and related publications

    Lancet Diabetes & Endocrinology

    Coskun T, et al. Retatrutide body-composition substudy. Coskun T, et al. Retatrutide body-composition substudy. Lancet Diabetes & Endocrinology. 2025. DOI: 10.1016/S2213-8587(25)00092-0. PMID: 40609566. https://pubmed.ncbi.nlm.nih.gov/40609566/(2025). DOI: 10.1016/S2213-8587(25

  8. P008Peer-reviewed human trials and related publications

    Lancet

    TRANSCEND-T2D-1 investigators. Phase 3 retatrutide in type 2 diabetes. TRANSCEND-T2D-1 investigators. Phase 3 retatrutide in type 2 diabetes. Lancet. 2026. DOI: 10.1016/S0140-6736(26)00967-0. PMID: 42250575. NCT06354660. https://pubmed.ncbi.nlm.nih.gov/42250575/(2026). DOI: 10.1016/S0140-6736(26

  9. P009Peer-reviewed human trials and related publications

    Diabetes, Obesity and Metabolism

    Giblin K, et al. TRIUMPH-1 through TRIUMPH-4 design, estimands, and multiplicity. Giblin K, et al. TRIUMPH-1 through TRIUMPH-4 design, estimands, and multiplicity. Diabetes, Obesity and Metabolism. 2026. DOI: 10.1111/dom.70209. PMID: 41090431. PMCID: PMC12673447. Design article; no results. https://pmc.ncbi.nlm.nih.gov/articles/PMC12673447/(2026). DOI: 10.1111/dom.70209

  10. P010Conference, sponsor-topline, and registry records

    Eli Lilly. TRIUMPH-1 ADA 2026 symposium presentation. Conference material; not peer reviewed. https://assets.ctfassets.net/mpejy6umgthp/26y2rux7lXdd3T6Uev6fcn/92e2edeb931298a4372dd804ec2382f9/TRIUMPH-1ADA2026Symposium.pdf

    Eli Lilly. TRIUMPH-1 ADA 2026 symposium presentation. Conference material; not peer reviewed. https://assets.ctfassets.net/mpejy6umgthp/26y2rux7lXdd3T6Uev6fcn/92e2edeb931298a4372dd804ec2382f9/TRIUMPH-1ADA2026Symposium.pdf(2026)

  11. P011Conference, sponsor-topline, and registry records

    Eli Lilly. TRIUMPH-1 sponsor topline and expanded disclosure. May–June 2026. Not peer reviewed. https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss

    Eli Lilly. TRIUMPH-1 sponsor topline and expanded disclosure. May–June 2026. Not peer reviewed. https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss(2026)

  12. P012Conference, sponsor-topline, and registry records

    Eli Lilly. TRIUMPH-2 and TRIUMPH-3 sponsor topline. July 23, 2026. Not peer reviewed. https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-successful-two-additional

    Eli Lilly. TRIUMPH-2 and TRIUMPH-3 sponsor topline. July 23, 2026. Not peer reviewed. https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-successful-two-additional(2026)

  13. P013Conference, sponsor-topline, and registry records

    Eli Lilly. TRIUMPH-4 sponsor topline. December 11, 2025. Not peer reviewed. https://investor.lilly.com/news-releases/news-release-details/retatrutide-delivered-significant-reductions-knee

    Eli Lilly. TRIUMPH-4 sponsor topline. December 11, 2025. Not peer reviewed. https://investor.lilly.com/news-releases/news-release-details/retatrutide-delivered-significant-reductions-knee(2025)

  14. P014Conference, sponsor-topline, and registry records

    ClinicalTrials.gov retatrutide study records and cross-registry audit. Registry evidence; result status varies by record. https://clinicaltrials.gov/api/v2/studies?query.term=AREA%5BInterventionName%5Dretatrutide%20OR%20AREA%5BInterventi...

    ClinicalTrials.gov retatrutide study records and cross-registry audit. Registry evidence; result status varies by record. https://clinicaltrials.gov/api/v2/studies?query.term=AREA%5BInterventionName%5Dretatrutide%20OR%20AREA%5BInterventionName%5DLY3437943&pageSize=100&format=json

  15. P015Regulatory records

    U.S. Food and Drug Administration. Concerns with unapproved GLP-1 products used for weight loss. Regulatory record. https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss

    U.S. Food and Drug Administration. Concerns with unapproved GLP-1 products used for weight loss. Regulatory record. https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss

  16. P016Identity, discovery, and analytical records

    Drug Testing and Analysis investigators. Analytical evaluation of three consumer-submitted vials labeled retatrutide. 2026. PMID: 42559975. PMCID: PMC13445994. https://pmc.ncbi.nlm.nih.gov/articles/PMC13445994/

    Drug Testing and Analysis investigators. Analytical evaluation of three consumer-submitted vials labeled retatrutide. 2026. PMID: 42559975. PMCID: PMC13445994. https://pmc.ncbi.nlm.nih.gov/articles/PMC13445994/(2026)

  17. P017Identity, discovery, and analytical records

    JAMA Network Open investigators. Marketplace availability survey; no product analysis. PMCID: PMC11703442. https://pmc.ncbi.nlm.nih.gov/articles/PMC11703442/

    JAMA Network Open investigators. Marketplace availability survey; no product analysis. PMCID: PMC11703442. https://pmc.ncbi.nlm.nih.gov/articles/PMC11703442/

  18. P018Regulatory records

    EMA, MHRA, Health Canada, TGA, Medsafe, and Ohio Board of Pharmacy records concerning investigational or unauthorized retatrutide/peptide products. Regulatory cluster; not efficacy evidence. See the evidence dossier source ledger for ind...

    EMA, MHRA, Health Canada, TGA, Medsafe, and Ohio Board of Pharmacy records concerning investigational or unauthorized retatrutide/peptide products. Regulatory cluster; not efficacy evidence. See the evidence dossier source ledger for individual records.

  19. P019Comparator trials — no outcome transfer

    STEP 1. Semaglutide obesity trial. DOI: 10.1056/NEJMoa2032183. PMID: 33567185. Comparator context only. https://doi.org/10.1056/NEJMoa2032183

    STEP 1. Semaglutide obesity trial. DOI: 10.1056/NEJMoa2032183. PMID: 33567185. Comparator context only. https://doi.org/10.1056/NEJMoa2032183. DOI: 10.1056/NEJMoa2032183

  20. P020Comparator trials — no outcome transfer

    SURMOUNT-1. Tirzepatide obesity trial. DOI: 10.1056/NEJMoa2206038. PMID: 35658024. Comparator context only. https://doi.org/10.1056/NEJMoa2206038

    SURMOUNT-1. Tirzepatide obesity trial. DOI: 10.1056/NEJMoa2206038. PMID: 35658024. Comparator context only. https://doi.org/10.1056/NEJMoa2206038. DOI: 10.1056/NEJMoa2206038

  21. P021Comparator trials — no outcome transfer

    SELECT. Semaglutide cardiovascular-outcomes trial. DOI: 10.1056/NEJMoa2307563. PMID: 37952131. Comparator context only. https://doi.org/10.1056/NEJMoa2307563

    SELECT. Semaglutide cardiovascular-outcomes trial. DOI: 10.1056/NEJMoa2307563. PMID: 37952131. Comparator context only. https://doi.org/10.1056/NEJMoa2307563. DOI: 10.1056/NEJMoa2307563

  22. P022Comparator trials — no outcome transfer

    SURPASS-CVOT. Tirzepatide cardiovascular-outcomes trial. DOI: 10.1056/NEJMoa2505928. PMID: 41406444. Comparator context only. https://doi.org/10.1056/NEJMoa2505928

    SURPASS-CVOT. Tirzepatide cardiovascular-outcomes trial. DOI: 10.1056/NEJMoa2505928. PMID: 41406444. Comparator context only. https://doi.org/10.1056/NEJMoa2505928. DOI: 10.1056/NEJMoa2505928

  23. P023Secondary and post-hoc reports — reused datasets

    Kanu et al. Appetite and eating behavior analysis. DOI: 10.1111/dom.70097. PMID: 40916752. Reuses NCT04867785. https://pmc.ncbi.nlm.nih.gov/articles/PMC12587234/

    Kanu et al. Appetite and eating behavior analysis. DOI: 10.1111/dom.70097. PMID: 40916752. Reuses NCT04867785. https://pmc.ncbi.nlm.nih.gov/articles/PMC12587234/. DOI: 10.1111/dom.70097

  24. P024Secondary and post-hoc reports — reused datasets

    Eating-behavior analysis in obesity. DOI: 10.1111/dom.16662. PMID: 40735804. Reuses NCT04881760. https://pubmed.ncbi.nlm.nih.gov/40735804/

    Eating-behavior analysis in obesity. DOI: 10.1111/dom.16662. PMID: 40735804. Reuses NCT04881760. https://pubmed.ncbi.nlm.nih.gov/40735804/. DOI: 10.1111/dom.16662

  25. P025Secondary and post-hoc reports — reused datasets

    Perceived-benefit exit interviews. PMID: 41216380. Qualitative sample from NCT04881760; not a trial. https://pmc.ncbi.nlm.nih.gov/articles/PMC12596213/

    Perceived-benefit exit interviews. PMID: 41216380. Qualitative sample from NCT04881760; not a trial. https://pmc.ncbi.nlm.nih.gov/articles/PMC12596213/

  26. P026Secondary and post-hoc reports — reused datasets

    Kidney-parameter post-hoc analysis. DOI: 10.1016/j.ekir.2025.03.049. PMID: 40630318. Reuses both Phase 2 trials. https://pmc.ncbi.nlm.nih.gov/articles/PMC12231004/

    Kidney-parameter post-hoc analysis. DOI: 10.1016/j.ekir.2025.03.049. PMID: 40630318. Reuses both Phase 2 trials. https://pmc.ncbi.nlm.nih.gov/articles/PMC12231004/(2025). DOI: 10.1016/j.ekir.2025.03.049

  27. P027Secondary and post-hoc reports — reused datasets

    ANGPTL3/8 analysis. DOI: 10.1111/dom.16661. PMID: 40726454. Stored-sample reanalysis. https://pubmed.ncbi.nlm.nih.gov/40726454/

    ANGPTL3/8 analysis. DOI: 10.1111/dom.16661. PMID: 40726454. Stored-sample reanalysis. https://pubmed.ncbi.nlm.nih.gov/40726454/. DOI: 10.1111/dom.16661

  28. P028Secondary and post-hoc reports — reused datasets

    Lipid and metabolomic analysis. DOI: 10.1210/clinem/dgag201. PMID: 42135195. Reuses both Phase 2 trials. https://doi.org/10.1210/clinem/dgag201

    Lipid and metabolomic analysis. DOI: 10.1210/clinem/dgag201. PMID: 42135195. Reuses both Phase 2 trials. https://doi.org/10.1210/clinem/dgag201. DOI: 10.1210/clinem/dgag201

  29. P029Secondary and post-hoc reports — reused datasets

    Cardiovascular-biomarker analysis. DOI: 10.1111/dom.71200. PMID: 42608321. Biomarkers only; no event outcome. https://pubmed.ncbi.nlm.nih.gov/42608321/

    Cardiovascular-biomarker analysis. DOI: 10.1111/dom.71200. PMID: 42608321. Biomarkers only; no event outcome. https://pubmed.ncbi.nlm.nih.gov/42608321/. DOI: 10.1111/dom.71200

  30. P030Secondary and post-hoc reports — reused datasets

    Blood-pressure and lipid meta-analysis. DOI: 10.1007/s40292-026-00812-6. PMID: 42371360. Derivative synthesis; no new participants. https://pubmed.ncbi.nlm.nih.gov/42371360/

    Blood-pressure and lipid meta-analysis. DOI: 10.1007/s40292-026-00812-6. PMID: 42371360. Derivative synthesis; no new participants. https://pubmed.ncbi.nlm.nih.gov/42371360/. DOI: 10.1007/s40292-026-00812-6

  31. P031Preclinical and patent context

    Marathe et al. and Cui et al. 2025 vendor-material oncology studies. Animal/ex-vivo evidence with incomplete material characterization; no human outcome transfer. PMCID: PMC11908972 and PMC11923992.

    Marathe et al. and Cui et al. 2025 vendor-material oncology studies. Animal/ex-vivo evidence with incomplete material characterization; no human outcome transfer. PMCID: PMC11908972 and PMC11923992.(2025)

  32. P032Peer-reviewed human trials and related publications

    Rationale, Design, and Baseline Characteristics of the TRANSCEND-CKD Trial of Retatrutide in Patients With Chronic Kidney Disease

    Heerspink HJL; van Raalte DH; Bjornstad P; Bunck MC; Wu P; Tunali I; Milicevic Z; Koeneman L. Nephrology Dialysis Transplantation. 2026;41(6):1058–1068. PMID: 41160422. PMCID: PMC13218929. NCT05936151.(2026). DOI: 10.1093/ndt/gfaf230

  33. P033Preclinical and patent context

    Lilly ADA 2021 preclinical poster and first-in-human presentation. Conference/sponsor material; the human dataset is superseded by P002.

    Lilly ADA 2021 preclinical poster and first-in-human presentation. Conference/sponsor material; the human dataset is superseded by P002.(2021)

  34. P034Preclinical and patent context

    Retatrutide patent family led by WO2019125938A1. Patent evidence; not clinical validation. https://patents.google.com/patent/WO2019125938A1/en

    Retatrutide patent family led by WO2019125938A1. Patent evidence; not clinical validation. https://patents.google.com/patent/WO2019125938A1/en