What Is Retatrutide?
A triple agonist targeting GLP-1, GIP, and glucagon receptors simultaneously — the first of its class to reach Phase 3 trials
Retatrutide (LY3437943) is an investigational once-weekly injectable drug developed by Eli Lilly and Company. It is a triple hormone receptor agonist that simultaneously activates the GLP-1, GIP, and glucagon receptors. It is not FDA-approved. Phase 3 TRIUMPH trials reported topline results in 2026 showing up to 28.3% mean body weight reduction at 80 weeks. Eli Lilly has announced plans for a Q1 2027 regulatory submission.
Retatrutide (LY3437943) is an investigational once-weekly injectable peptide developed by Eli Lilly. It is the first drug in clinical development to simultaneously activate three metabolic hormone receptors: GLP-1 (glucagon-like peptide-1), GIP (glucose-dependent insulinotropic polypeptide), and glucagon. This triple agonism distinguishes it from earlier GLP-1 agonists and dual GLP-1/GIP agonists like tirzepatide.
The three receptors it targets
Retatrutide's defining characteristic is its simultaneous activation of three distinct hormone receptors, each contributing a different metabolic effect.
GLP-1 receptor agonism slows gastric emptying, reduces appetite, and stimulates glucose-dependent insulin secretion. This is the mechanism shared with semaglutide and tirzepatide.
GIP receptor agonism potentiates insulin secretion and may reduce the GI side effects associated with GLP-1 agonism alone. Tirzepatide also targets this receptor; retatrutide adds glucagon on top.
Glucagon receptor agonism increases basal metabolic rate and promotes hepatic fat oxidation. This is the novel addition in retatrutide — no currently approved obesity drug targets the glucagon receptor. It is the likely driver of the greater weight loss observed versus dual agonists.
Clinical development history
Retatrutide entered clinical development in 2020. The Phase 2 dose-escalation trial (NCT04881760) published in the New England Journal of Medicine in 2023 established the efficacy and safety profile that advanced it to Phase 3.
What makes it different from semaglutide and tirzepatide
The key distinction is the glucagon receptor component. Semaglutide (Ozempic/Wegovy) is a GLP-1 agonist. Tirzepatide (Mounjaro/Zepbound) adds GIP. Retatrutide adds glucagon on top of both — creating a mechanism that appears to drive meaningfully greater weight loss than either predecessor.
Phase 2 data: Jastreboff et al., NEJM 2023. Phase 3 topline: Eli Lilly press release, 2026. All figures are from published or announced clinical trial data — not anecdote.
Common Questions About Retatrutide
Is retatrutide a GLP-1?
Yes — retatrutide activates the GLP-1 receptor, but it also activates the GIP and glucagon receptors simultaneously. This makes it a triple agonist, not a GLP-1 single agonist like semaglutide (Ozempic/Wegovy). The glucagon receptor component is what distinguishes retatrutide from tirzepatide, which is a dual GLP-1/GIP agonist.
What does GLP-3 mean?
GLP-3 is an informal shorthand sometimes used in online communities to describe retatrutide's triple-receptor mechanism (GLP-1 + GIP + glucagon). It is not an official pharmacological term. The correct designation is “triple GLP-1/GIP/glucagon receptor agonist.” GLP-3 does not refer to a distinct hormone or receptor in the scientific literature. See Is Retatrutide a GLP-1 or GLP-3? for a full explanation.
When could retatrutide become available?
Following TRIUMPH-1 topline results (May 21, 2026), Eli Lilly announced plans for a Q1 2027 regulatory submission to the FDA. Standard review takes approximately 10–12 months from acceptance. Approval and commercial availability are not guaranteed. See When Will Retatrutide Be Available? for the full timeline. The only current legal access path is through an authorized clinical trial.