Retatrutide: Chemical Properties
17 PubMed CitationsExpert ReviewedGMP CertifiedLast Reviewed: February 2026
Chemical Properties
| Molecular Formula | C₂₂₁H₃₄₂N₄₆O₆₈ |
| Molecular Weight | 4731.33 Da |
| CAS Number | 2381089-83-2 |
| PubChem CID | 171390338 |
| Sequence (1-Letter) | Y-Aib-QGTFTSDYSI-αMeL-LDK-K*-AQ-Aib-AFIEYLLEGGPSSGAPPPS-NH₂ (* = Lys modified with AEEA-γGlu-C20 diacid) |
| Sequence (3-Letter) | Tyr-Aib-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-αMeLeu-Leu-Asp-Lys-Lys(AEEA-γGlu-C20 diacid)-Ala-Gln-Aib-Ala-Phe-Ile-Glu-Tyr-Leu-Leu-Glu-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH₂ |
| Structure | 39-amino acid linear peptide; GIP backbone; non-coded residues: Aib at positions 2 & 20, α-methyl-L-leucine at position 13; C20 fatty diacid conjugated at Lys-17 via AEEA-γGlu linker; C-terminus amidated |
| Origin | Synthetic peptide engineered from GIP (glucose-dependent insulinotropic polypeptide) backbone; developed by Eli Lilly and Company |
| Classification | Triple Incretin/Hormone Receptor Agonist (GLP-1/GIP/Glucagon) / Acylated Peptide / Investigational Drug |
| Half-Life | Approximately 6 days in humans, supporting once-weekly dosing |
| Bioavailability | Subcutaneous injection; Tmax 12–72 hours; albumin binding via C20 fatty diacid extends duration of action |
Identifiers
| Purity Standard | ≥99% by RP-HPLC (research grade) |
| Synonyms | Retatrutide, LY3437943, LY-3437943, RTT, GGG Tri-Agonist, Triple G, Triple Agonist, Reta Peptide |
| InChI Key | MLOLQJNKXBNWFW-JMUPIODPSA-N |
| Developer | Eli Lilly and Company (Indianapolis, IN, USA) |
References
- Jastreboff AM, Kaplan LM, Frias JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. New England Journal of Medicine, 389(6), 514-526, 2023.
- Rosenstock J, Frias J, Jastreboff AM, Du Y, Lou J, Gurbuz S, Thomas MK, Hartman ML, Haupt A, Milicevic Z, Coskun T. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. Lancet, 402(10401), 529-544, 2023.
- Sanyal AJ, Kaplan LM, Frias JP, Brouwers B, Wu Q, Thomas MK, Harris C, Schloot NC, Du Y, Mather KJ, Haupt A, Hartman ML. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine, 30(7), 2037-2048, 2024.
- Coskun T, Urva S, Roell WC, Qu H, Loghin C, Moyers JS, O'Farrell LS, Briere DA, Sloop KW, Thomas MK, Pirro V, Wainscott DB, Willard FS, Abernathy M, Morford L, Du Y, Benson C, Gimeno RE, Haupt A, Milicevic Z. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metabolism, 34(9), 1234-1247.e9, 2022.
- Giblin K, Kaplan LM, Somers VK, Le Roux CW, Hunter DJ, Wu Q, Lalonde A, Ahmad N, Bethel MA. Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials. Diabetes, Obesity and Metabolism, 28(1), 83-93, 2026.
- Coskun T, Wu Q, Schloot NC, Haupt A, Milicevic Z, Khouli C, Harris C. Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial. The Lancet Diabetes & Endocrinology, 13(8), 674-684, 2025.
- Heerspink HJL, Lu Z, Du Y, Duffin KL, Coskun T, Haupt A, Hartman ML. The Effect of Retatrutide on Kidney Parameters in Participants With Type 2 Diabetes Mellitus and/or Obesity. Kidney International Reports, 10(6), 1980-1992, 2025.
- Urva S, Coskun T, Loh MT, Du Y, Thomas MK, Gurbuz S, Haupt A, Benson CT, Hernandez-Illas M, D'Alessio DA, Milicevic Z. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet, 400(10366), 1869-1881, 2022.
- Heerspink HJL, van Raalte DH, Bjornstad P, Bunck MC, Wu P, Tunali I, Milicevic Z, Koeneman L. Rationale, design and baseline characteristics of the TRANSCEND-CKD trial of retatrutide in patients with chronic kidney disease. Nephrology Dialysis Transplantation, gfaf230, 2025.
- Katsi V, Koutsopoulos G, Fragoulis C, Dimitriadis K, Tsioufis K. Retatrutide - A Game Changer in Obesity Pharmacotherapy. Biomolecules, 15(6), 796, 2025.
- Abdul-Rahman T, Roy P, Ahmed FK, Mueller-Gomez JL, Sarkar S, Garg N, Femi-Lawal VO, Wireko AA, Thaalibi HI, Hashmi MU, Dzebu AS, Banimusa SB, Sood A. The power of three: Retatrutide's role in modern obesity and diabetes therapy. European Journal of Pharmacology, 985, 177095, 2024.
- Maharshi V, Singh S, Manjhi PK, Singh SK, Kumar A, Kumar R. Navigating retatrutide safety: comprehensive insights from systematic review and meta-analysis. Journal of Public Health and Development, 24(1), 318-338, 2026.
- Abouelmagd AA, Abdelrehim AM, Bashir MN, Abdelsalam F, Marey A, Tanas Y, Abuklish DM, Belal MM. Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist for obesity treatment: a systematic review and meta-analysis of randomized controlled trials. Proceedings (Baylor University Medical Center), 38(3), 291-303, 2025.
- Marathe SJ, Grey EW, Bohm MS, Joseph SC, Ramesh AV, Cottam MA, et al. Incretin triple agonist retatrutide (LY3437943) alleviates obesity-associated cancer progression. NPJ Metabolic Health and Disease, 3(1), 10, 2025.
- Ma J, Hu X, Zhang W, Tao M, Wang M, Lu W. Comparison of the effects of Liraglutide, Tirzepatide, and Retatrutide on diabetic kidney disease in db/db mice. Endocrine, 87(1), 159-169, 2025.
- Tewari J, Qidwai KA, Tewari A, Kaur S, Tewari V, Maheshwari A. Efficacy and safety of triple hormone receptor agonist retatrutide for the management of obesity: a systematic review and meta-analysis. Expert Review of Clinical Pharmacology, 18(1-2), 51-66, 2025.
- Urva S, O'Farrell L, Du Y, Loh MT, Hemmingway A, Qu H, Alsina-Fernandez J, Haupt A, Milicevic Z, Coskun T. The novel GIP, GLP-1 and glucagon receptor agonist retatrutide delays gastric emptying. Diabetes, Obesity and Metabolism, 25(11), 2784-2788, 2023.
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