Description
Retatrutide is a 39-residue, lipid-modified peptide specifically designed to activate three class B GPCRs: the GLP-1 receptor, the glucose-dependent insulinotropic polypeptide (GIP) receptor, and the glucagon receptor. Structural work using cryo-EM has shown that retatrutide engages conserved peptide-binding motifs on each receptor while also inducing receptor-specific conformations that support simultaneous triple agonism.
In metabolic research, retatrutide is employed as a tool compound for obesity, diabetes, and NAFLD/NASH models. Phase 2 clinical studies have reported large reductions in body weight and improvements in glycemic control and liver-fat markers, making it a benchmark molecule for exploring multi-receptor incretin pharmacology. Preclinical and translational experiments assess endpoints such as body-weight trajectories, energy expenditure, lipid handling, hepatic fat content, and pancreatic islet function.
