Educational reference, not medical advice. This page summarizes information from published research and regulatory filings for educational purposes. It is not a recommendation to use any compound and should not replace guidance from a licensed healthcare provider. Most peptides discussed here are not approved for the uses described.
What it is
Retatrutide — Eli Lilly's experimental code name LY3437943 — is a synthetic 39-amino-acid peptide engineered to activate three metabolic hormone receptors at once: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon. It is the first triple agonist in this class to advance into late-stage trials. Like tirzepatide, the molecule carries a fatty acid side chain that binds it to albumin, extending the half-life enough for once-weekly subcutaneous dosing.
The drug is sometimes described informally as a "triagonist" or "trizepatide" but those names are not used by Lilly.
History
Lilly disclosed retatrutide's chemistry in 2022 and reported Phase I single- and multiple-ascending-dose data the same year. The Phase II obesity trial (Jastreboff et al., NEJM 2023) randomized 338 adults with obesity to placebo or one of several retatrutide doses through 48 weeks. At the 12 mg weekly dose, the least-squares mean change in body weight was −24.2% versus −2.1% on placebo. A parallel Phase II trial in type 2 diabetes (Rosenstock et al., Lancet 2023) reported HbA1c reductions exceeding 2 percentage points at the highest dose. In 2024, a Phase II read-out in MASH/MASLD showed liver-fat reductions of more than 80% in many participants at the higher doses.
The Phase III program — branded TRIUMPH — covers obesity, type 2 diabetes, obstructive sleep apnea, knee osteoarthritis, and cardiovascular outcomes. Top-line results from the obesity arm are expected in 2025–2026.
Regulatory status
Retatrutide is not approved anywhere in the world. It is an investigational compound available only through registered clinical trials. The molecule is not in any compounding pharmacy's legitimate supply chain — any vial labeled "retatrutide" sold for research is unregulated and not verified against Lilly's reference standard.
Mechanism
The three receptors are believed to contribute distinct but complementary effects:
- GLP-1 receptor activation drives glucose-dependent insulin release, glucagon suppression, slowed gastric emptying, and central appetite reduction.
- GIP receptor activation appears to improve insulin sensitivity in adipose tissue and may reduce GI side effects relative to pure GLP-1 agonism.
- Glucagon receptor activation raises resting energy expenditure and promotes hepatic fat oxidation — the proposed explanation for retatrutide's outsized effects on liver fat and total body weight.
The glucagon arm is the most contentious. Glucagon raises blood glucose in isolation, but in the context of strong GLP-1 stimulation the net effect on glucose has been favorable in Phase II trials.
Half-life and dosing intervals
The published terminal half-life is approximately 6 days, supporting once-weekly subcutaneous injection. Steady-state plasma concentrations are reached after roughly 4 to 6 weeks of consistent dosing.
In the Phase II obesity trial, doses were escalated monthly to manage gastrointestinal side effects. The schedule for the 12 mg target dose was: 2 mg weekly for 4 weeks → 4 mg → 8 mg → 12 mg maintenance. Lower target doses (1, 4, and 8 mg) used shorter or shallower escalations. The 12 mg dose produced the largest weight loss but also the highest rate of GI adverse events.
There is no established outside-of-trial dose. Research-grade material sold online is not validated and the long-term safety profile in humans has not been characterized.
Reconstitution example
Research-grade retatrutide is typically supplied lyophilized in 5 mg, 10 mg, or 20 mg vials.
A 10 mg vial reconstituted with 2 mL of bacteriostatic water yields a concentration of 5 mg/mL. On a 1 mL U-100 insulin syringe, 4 units (0.04 mL) contains 0.2 mg and 40 units (0.4 mL) contains 2 mg — the lowest dose tested in the Phase II trial. Vial's calculator handles unit-to-mg conversion automatically.
What to know
- Investigational only. No regulator has reviewed retatrutide's full safety package. The Phase II dataset covers fewer than 350 obesity participants over 48 weeks.
- Largest reported weight loss. The 24.2% mean reduction at 48 weeks in the Phase II obesity trial exceeds the figures reported for semaglutide (about 15%) and tirzepatide (about 21%) at comparable timepoints, though no head-to-head trial has been completed.
- Heart rate. Phase II data showed dose-dependent heart rate increases that peaked at 24 weeks and partially resolved through week 48. Long-term cardiovascular effects are the subject of ongoing trials.
- GI side effects. Nausea, vomiting, and diarrhea were the dominant adverse events, concentrated during escalation.
- Storage. Lyophilized peptide is best stored refrigerated and protected from light. Once reconstituted, refrigerate and use within the stability window specified by the supplier.
Sources
- 1.Jastreboff AM et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine.
- 2.Rosenstock J et al. (2023). 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. The Lancet.
- 3.Sanyal AJ et al. (2024). Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease. Nature Medicine.
- 4.Abdul-Rahman T et al. (2024). The power of three: Retatrutide's role in modern obesity and diabetes therapy. European Journal of Pharmacology.