Most compounds in this category act on a single receptor. Retatrutide was engineered to act on three at once.
Retatrutide
Retatrutide, development code LY3437943, is a single synthetic peptide conjugated to a fatty diacid moiety. It acts as an agonist at three receptors simultaneously: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon. Cell culture work indicates it is less potent than the endogenous ligands at the human glucagon and GLP-1 receptors, and considerably more potent at the GIP receptor. Its pharmacokinetics are dose-proportional, with a reported half-life of approximately six days.
Retatrutide is described in the literature as the first single peptide with triple receptor agonist activity to reach this stage of investigation. It follows tirzepatide, the GLP-1/GIP dual agonist, as the next step in incretin-based research. The interest in adding glucagon receptor activity is mechanistic: preclinical work indicated the compound influences both energy intake and energy expenditure, rather than intake alone.
Phase 2 data has been published in both obesity and type 2 diabetes cohorts, reporting mean body weight reduction of 24.2% at 48 weeks in the obesity study and 16.9% at 36 weeks in the diabetes study. A separate phase 2a substudy examined hepatic fat in participants with metabolic dysfunction-associated steatotic liver disease. First phase 3 results, TRIUMPH-1 and TRANSCEND-T2D-1, were presented at the American Diabetes Association Scientific Sessions in June 2026.