Retatrutide

Retatrutide (LY3437943) is a high-purity synthetic peptide (99.5%) designed to act as a triple receptor agonist for glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors. Structurally, the molecule forms a single, continuous alpha-helical conformation that allows its N-terminal region to interact with receptor transmembrane domains, while the C-terminal region engages extracellular portions of the GLP-1 and GIP receptors. Retatrutide shows varying receptor potency, with EC50 values of 0.0643 nM for the human GIP receptor, 0.775 nM for the GLP-1 receptor, and 5.79 nM for the glucagon receptor.

Pharmacologically, retatrutide exhibits dose-dependent activity and an estimated half-life of approximately six days. It is primarily metabolized by the liver and does not demonstrate meaningful interactions with cytochrome P450 enzymes. Activation of its target receptors produces significant metabolic effects, including decreased gastric emptying and reduced food intake, which in turn lead to improvements in body weight regulation and glycated hemoglobin levels in experimental models.