Retatrutide
GLP-1/GIP/Glucagon Triple Receptor Agonist
Retatrutide is the world's first GLP-1/GIP/glucagon triple receptor agonist to enter advanced clinical study. By engaging three distinct metabolic pathways simultaneously, it has generated unprecedented body composition data in published trials. It represents the next evolution beyond dual-agonist peptides like tirzepatide.
Aliases: LY3437943, Triple agonist
- Research score
- 7/10
Key fact
First-ever GIP/GLP-1/glucagon triple receptor agonist. Up to 24.2% body weight loss in Phase 2 (NEJM). 72% prediabetes reversal. Phase 3 TRIUMPH underway.
Mechanism
Retatrutide (LY3437943) is a single polypeptide conjugated to a fatty diacid moiety that activates GIP, GLP-1, and glucagon receptors. The triple agonism provides complementary metabolic benefits: GLP-1 reduces appetite and slows gastric emptying, GIP enhances insulin sensitivity and may promote fat storage efficiency, and glucagon receptor activation increases hepatic fat oxidation, energy expenditure, and thermogenesis. The glucagon component also significantly reduces hepatic steatosis, with Phase 2 data showing near-complete resolution of MASLD/MASH in some participants.
Evidence note
Emerging — Phase 2 complete with remarkable results (24.2% weight loss). Phase 3 (TRIUMPH program by Eli Lilly) underway. Not yet FDA-approved. Very promising but limited to one major Phase 2 trial published.
Studies
Triple hormone receptor agonist retatrutide for MASLD
Significant liver fat reduction; potential MASH resolution in Phase 2 participants
Open sourceTriple-Hormone-Receptor Agonist Retatrutide for Obesity — Phase 2 Trial
Up to 24.2% weight loss at 48 weeks; 72% of prediabetic participants reverted to normoglycemia
Open sourceRetatrutide — A Game Changer in Obesity Pharmacotherapy
Potent activation of all three receptors (GIP/GLP-1/glucagon); significant weight reduction and metabolic improvements
Open source
FAQ
Is retatrutide FDA-approved?
Not yet. Phase 2 is complete with remarkable results. Phase 3 (TRIUMPH program by Eli Lilly) is currently underway. It is the most advanced triple agonist candidate in development.
Can retatrutide help with fatty liver (NAFLD/MASH)?
Phase 2 data published in Nature Medicine showed significant liver fat reduction, with near-complete MASLD/MASH resolution in some participants. The glucagon receptor component specifically drives hepatic fat oxidation — an effect unique to triple agonists.
How does retatrutide compare to tirzepatide?
Retatrutide is a triple agonist (GIP + GLP-1 + glucagon) while tirzepatide is a dual agonist (GIP + GLP-1). The added glucagon receptor activation drives hepatic fat oxidation and energy expenditure. Phase 2 data showed up to 24.2% weight loss vs tirzepatide's 22.5% in separate trials.
For research and educational use only. This content is not medical advice.