Retatrutide Reta retatrutide

Retatrutide (USAN, INN; code LY3437943; CAS 2381089-83-2) is a synthetic 39-amino acid peptide with the molecular formula C₂₂₁H₃₄₂N₄₆O₆₈ and a molecular weight of approximately 4731.3 g/mol. Engineered from a GIP backbone, it incorporates three non-coded residues (Aib², α-Me-Leu¹³, Aib²⁰) and features a C20 fatty diacid conjugated via a γ-glutamic acid and AEEA linker, enabling reversible albumin binding for extended half-life, with an amidated C-terminus. As a first-in-class unimolecular triple agonist, Retatrutide simultaneously targets the glucose-dependent insulinotropic polypeptide receptor (GIPR), glucagon-like peptide-1 receptor (GLP-1R), and the glucagon receptor (GCGR), thereby integrating complementary metabolic actions: GIPR and GLP-1R activation enhances glucose-dependent insulin secretion and suppresses appetite, while GCGR agonism increases energy expenditure and directly promotes lipolysis, resulting in superior glycemic control and weight loss compared to dual agonists.