Quick summary
Retatrutide is Eli Lilly's investigational triple receptor agonist targeting GLP-1, GIP, and glucagon. It has produced up to 28.7% weight loss in Phase 3 trials, the largest reduction recorded for any obesity drug, and is not yet FDA-approved.
Overview
Retatrutide (LY3437943) is Eli Lilly's investigational triple hormone receptor agonist targeting GLP-1, GIP, and glucagon receptors simultaneously. In Phase 3 trials it has demonstrated weight loss of up to 28.7% at 12 mg weekly — the largest body weight reduction recorded for any pharmacological obesity treatment to date.
Mechanism of action
Retatrutide activates three complementary hormone receptors in a single molecule. GLP-1 receptor agonism slows gastric emptying, suppresses appetite via hypothalamic satiety pathways, and stimulates glucose-dependent insulin secretion. GIP receptor agonism potentiates GLP-1-driven insulin release, improves beta-cell function, and may reduce GLP-1-associated nausea. Glucagon receptor agonism increases hepatic glucose output and stimulates thermogenesis — effects that would raise blood glucose in isolation but are counterbalanced by the insulinotropic GLP-1/GIP axes. The net metabolic result is pronounced energy deficit, enhanced fat oxidation, and superior weight loss versus dual-agonists. A C18 fatty acid chain binds reversibly to serum albumin, extending the half-life to ~6 days and enabling once-weekly subcutaneous dosing.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| obesity / weight loss (clinical trial protocol) | subcutaneous | 2–12 mg | once weekly | Phase 3 protocols titrated from 2 mg weekly, increasing every 4 weeks to target doses of 8 mg or 12 mg. Slower titration reduces GI side effects. |
| type 2 diabetes management (clinical trial protocol) | subcutaneous | 4–8 mg | once weekly | Clinical trial data at 4–8 mg weekly showed A1C reductions up to 2.0%. Titration from 2 mg weekly over 12–16 weeks. |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
Phase 2 data (NEJM, 2023) showed 24.2% weight reduction at 24 weeks with 12 mg weekly dosing. Phase 3 TRIUMPH-4 trial reported 26.4–28.7% weight loss at 40 weeks depending on dose. TRANSCEND-T2D-1 Phase 3 trial met primary and all secondary endpoints for A1C reduction and weight loss in type 2 diabetes. Phase 3 results for MASH (metabolic steatohepatitis) are pending. No FDA approval as of April 2026.[1][2][3][4]
Evidence grading
Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.
Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with Retatrutide for synergistic effects.
Legal status
Retatrutide is an investigational drug (IND) under active Phase 3 development by Eli Lilly. It is not FDA-approved and not legally available outside clinical trials in the US. Research chemical suppliers offer compounded or synthesized versions without regulatory oversight; quality and safety cannot be verified.
Sourcing & access
Research compound
Retatrutide is classified as a research compound. Regulatory status varies by jurisdiction. Always verify current legal status and source from vendors providing third-party certificates of analysis (COA).
Frequently asked questions
Retatrutide (LY3437943) is Eli Lilly's investigational triple hormone receptor agonist targeting GLP-1, GIP, and glucagon receptors in a single molecule. It is in Phase 3 clinical development for obesity and type 2 diabetes.
It activates three complementary hormone receptors. GLP-1 agonism suppresses appetite and slows gastric emptying, GIP agonism potentiates insulin release and may reduce nausea, and glucagon agonism increases hepatic glucose output and stimulates thermogenesis, driving a pronounced energy deficit and fat oxidation.
Phase 2 data published in NEJM showed 24.2% weight reduction at 24 weeks with 12 mg weekly. The Phase 3 TRIUMPH-4 trial reported 26.4 to 28.7% weight loss at 40 weeks depending on dose, the largest reduction recorded for any pharmacological obesity treatment.
No. As of April 2026 retatrutide is an investigational drug under active Phase 3 development and is not FDA-approved. It is not legally available outside clinical trials in the US.
Phase 3 obesity protocols titrate from 2 mg weekly subcutaneously, increasing every 4 weeks to target doses of 8 mg or 12 mg. Slower titration is used to reduce gastrointestinal side effects.
Retatrutide has a half-life of approximately 6 days. A C18 fatty acid chain attached to the peptide binds reversibly to serum albumin, slowing renal clearance and extending duration of action. This albumin-binding strategy enables once-weekly subcutaneous dosing at 2 to 12 mg and produces steady plasma levels across the dosing interval.
The most common side effects are gastrointestinal and dose-dependent: nausea, vomiting, diarrhea, constipation, and decreased appetite. Injection site reactions, hypoglycemia when combined with insulin or sulfonylureas, and a GLP-1 class warning for thyroid C-cell effects have also been noted.
Research references
- Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 TrialPubMed
- 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 trialPubMed
- Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trialsPubMed
- Effects of once-weekly subcutaneous retatrutide on weight and metabolic markers: A systematic review and meta-analysis of randomized controlled trialsPubMed