Retatrutide

What Is Retatrutide?

Retatrutide (LY3437943) is a long-acting peptide agonist of three metabolic receptors at once: the GLP-1 receptor (appetite suppression and slowed gastric emptying), the GIP receptor (amplified insulin response, thought to soften GLP-1-associated nausea), and the glucagon receptor, which the earlier incretin drugs avoided and which drives hepatic fat oxidation and raises total energy expenditure. The glucagon arm is what distinguishes retatrutide from semaglutide and tirzepatide: alongside reduced intake, energy expenditure increases.

Receptor binding studies show retatrutide is most potent at GIP (EC50 about 0.06 nM) with balanced activity at GLP-1 and glucagon receptors, and structural work published in Cell Discovery (2024) shows it engages all three GPCRs through a conserved core sequence built from the GIP and glucagon backbones. In the Phase 2 obesity trial published in the New England Journal of Medicine (2023), participants at the highest dose lost a mean of 24.2% of body weight at 48 weeks, exceeding the reductions reported for semaglutide and tirzepatide over comparable periods. Eli Lilly's TRIUMPH Phase 3 programme is ongoing and the compound is not approved in any market.