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.
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.
Where to get it
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