GIP/GLP-1/Glucagon Triple Receptor Agonist
Retatrutide
Also known as: GLP-3 RT, LY3437943
An investigational triple hormone-receptor agonist (GIP, GLP-1, and glucagon receptors) from Eli Lilly, showing the largest reported weight-loss effect of the major incretin-class drugs in Phase 2 data — not yet FDA-approved. Sold under the coded name 'GLP-3 RT.'
A note on naming and regulatory status
Retatrutide (LY3437943) is genuinely different from semaglutide and tirzepatide in one important respect: it is not FDA-approved for any indication. It remains an investigational drug in Eli Lilly's development pipeline. The vendor code name "GLP-3 RT" ("RT" for retatrutide) is sold as a research chemical, which — unlike the semaglutide/tirzepatide situation — is not simply an unregulated version of an otherwise-approved drug; it's a compound that hasn't cleared Phase 3 trials or received any approval decision at all as of this writing.
Overview
Retatrutide is a triple agonist, activating GIP, GLP-1, and glucagon receptors simultaneously — one mechanistic step beyond tirzepatide's dual-agonism. The added glucagon receptor activity is proposed to increase energy expenditure on top of the appetite-suppressing effects shared with the other incretin-class drugs.
Proposed Mechanism of Action
In addition to GIP and GLP-1 receptor effects shared with tirzepatide, glucagon receptor agonism is associated with increased hepatic glucose output and energy expenditure — the combination is the proposed basis for retatrutide's larger reported weight-loss effect relative to dual or single-receptor agonists, though this mechanism also raises distinct questions (e.g., effects on blood glucose from the glucagon component) that are still being characterized.
Research Context
The cited Phase 2 trial randomized 338 adults with obesity to escalating doses (1, 4, 8, or 12 mg) of once-weekly retatrutide or placebo for 48 weeks. At the highest dose (12 mg), mean weight reduction reached 24.2% at 48 weeks — larger than the corresponding-duration results reported for semaglutide or tirzepatide in their own pivotal trials, though again, this is a cross-trial comparison, not a head-to-head trial.
Limitations of the Current Evidence
- This is Phase 2 data — a dose-finding and early efficacy/safety trial, not the larger, longer Phase 3 program (already underway per public trial registries) that would typically precede an approval decision.
- As an investigational compound with no approved formulation, there is no FDA-regulated reference product to compare "research use only" retatrutide against — unlike semaglutide or tirzepatide, there's no pharmacy-grade version at all right now.
- The added glucagon-receptor mechanism is newer and less characterized in long-term human data than GLP-1/GIP agonism alone.
Research-Setting Dosing (as reported in literature)
| Route | Range (as reported) | Frequency | Notes |
|---|---|---|---|
| Subcutaneous injection | 1–12 mg | Once weekly | Phase 2 trial (Jastreboff et al., 2023), 48 weeks. At the 12 mg dose, mean weight reduction was 24.2% versus 2.1% for placebo; effects were clearly dose-dependent across the 1, 4, 8, and 12 mg groups tested. |
Figures above are extracted directly from the cited preclinical/research literature. They describe what researchers administered to study subjects (frequently animal models) — they are not human dosing recommendations and are not medical advice.
Cited Studies
Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial
Jastreboff AM, Kaplan LM, Frías JP, et al. · New England Journal of Medicine · 2023
Human clinical trial (Phase 2, randomized, double-blind, placebo-controlled, 338 subjects)View source →
Last updated August 1, 2026