What Is Retatrutide?
Retatrutide (LY3437943) is a once-weekly injectable triple agonist of GLP-1, GIP, and glucagon receptors developed by Eli Lilly and currently in Phase 3 clinical trials. It represents the next frontier beyond tirzepatide (dual GLP-1/GIP), adding glucagon receptor agonism that increases energy expenditure and hepatic fat reduction. Phase 2 results show weight losses approaching 25% of body weight at 48 weeks — among the highest ever documented for a pharmacological intervention.
Triple Receptor Mechanism
GLP-1 receptor agonism provides appetite suppression, reduced gastric emptying, and glucose-dependent insulin release. GIP receptor agonism enhances insulin secretion, improves beta cell function, and may reduce GLP-1-associated nausea. Glucagon receptor agonism increases energy expenditure through thermogenesis, drives hepatic fat oxidation (addressing NASH), and — in the context of simultaneous GLP-1 activity — does not produce dangerous hyperglycemia. The three mechanisms are complementary and largely non-overlapping.
Clinical Data
At the highest dose (12mg weekly), retatrutide produced 24.2% mean weight loss at 48 weeks. At lower doses, the compound showed 17–22% weight loss with a favorable safety profile dominated primarily by the expected GI side effects shared with all GLP-1 agonists. Phase 3 trials are ongoing for obesity and T2D.
Quick Reference
Member reference tables summarize the compound's research parameters.
Research Indications
Research Protocols
As reported in cited literature and research-community logs (see Research Citations below), not a personal dosing recommendation.
This member section describes parameters reported in the research literature.
Peptide Interactions
This member section summarizes reported compound interactions and evidence limitations.
Reported Research Time Points
This member section summarizes reported research time points.
Safety Notes
Included for harm-reduction awareness only, in the event this compound is encountered outside its labeled research use. Inclusion here does not imply RUO Codes endorses, recommends, or instructs human use.
This member section discusses research safety considerations and uncertainties.
Quality Indicators
Research Citations
- Lilly's triple agonist, retatrutide, drove substantial improvements in weight, A1C, knee osteoarthritis pain, and obstructive sleep apnea (ADA 86th Scientific Sessions)
Eli Lilly and Company, 2026, Press Release - Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (TRIUMPH-1)
Eli Lilly and Company, 2026, Press Release - Lilly's triple agonist, retatrutide, demonstrated significant reductions in A1C and weight in first Phase 3 trial for treatment of type 2 diabetes (TRANSCEND-T2D-1)
Eli Lilly and Company, 2026, Press Release - Lilly reports first-quarter 2026 financial results, raises full year guidance and highlights momentum of new medicines
Eli Lilly and Company, 2026, Press Release - Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials
Giblin K, et al., 2026, Diabetes, Obesity and Metabolism - Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial (TRIUMPH-4)
Eli Lilly and Company, 2025, Press Release - Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial
Jastreboff, A.M., Aronne, L.J., Ahmad, N.N., et al., 2023, New England Journal of Medicine - Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, phase 2 trial conducted in the USA
Rosenstock, J., Frias, J., Jastreboff, A.M., et al., 2023, The Lancet - Efficacy and safety of retatrutide for treatment of people with obesity and metabolic dysfunction-associated steatotic liver disease: a randomised, double-blind, placebo-controlled, phase 2 trial
Sanyal, A.J., Cusi, K., Hartman, M.L., et al., 2024, Nature Medicine - Structural insights into triple agonism at GLP-1R, GIPR and GCGR by retatrutide
Li, W., Xu, Y., Wang, M., et al., 2024, Cell Discovery - LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept
Coskun, T., Sloop, K.W., Loghin, C., et al., 2022, Cell Metabolism - 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
Urva, S., Coskun, T., Loh, M.T., et al., 2023, The Lancet - Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial
Jastreboff AM, Kaplan LM, Frías JP, 2023, N Engl J Med - Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity
Drucker DJ, 2024, Diabetes Care - Gut hormones and appetite regulation
Hong SH, Choi KM, 2024, Curr Opin Endocrinol Diabetes Obes - Emerging pharmacotherapies for obesity: A systematic review
Kokkorakis M, Chakhtoura M, Rhayem C, 2025, Pharmacol Rev - Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials
Giblin K, Kaplan LM, Somers VK, 2026, Diabetes Obes Metab