Compound Profile: Retatrutide

Retatrutide (LY3437943) is a synthetic linear peptide of 39 amino acids with the molecular formula C221H342N46O68 and an average molecular weight of approximately 4,731 g/mol. Like tirzepatide it is built on a GIP-derived backbone with Aib substitutions for protease resistance, and it carries a C20 fatty-diacid side chain on a lysine residue for albumin binding and extended half-life.

The feature that defines retatrutide in the literature is activity at the glucagon receptor in addition to the GIP and GLP-1 receptors. Published in-vitro characterisation describes it as a potent GIP receptor agonist with lower, but meaningful, activity at the GLP-1 and glucagon receptors. Glucagon receptor agonism is of research interest for its effects on hepatic energy expenditure and lipid metabolism, and the central question in much of the comparative work is what this third activity adds to dual agonism.

Semaglutide is a single GLP-1 receptor agonist of 31 residues. Tirzepatide adds GIP receptor activity in a 39-residue peptide. Retatrutide adds glucagon receptor activity in a 39-residue peptide of similar size and lipidation. The three are therefore a natural series for comparative pharmacology, and a substantial part of the recent literature consists of head-to-head work in receptor assays and preclinical metabolic models.

Research on retatrutide concentrates on multi-receptor signalling in cell lines; hepatic steatosis and lipid metabolism in rodent models, where glucagon receptor activity is of particular interest; energy expenditure and adiposity models; and a clinical trial programme that is more recent and smaller than tirzepatide's but widely referenced. The compound is not approved as a medicine at the time of writing.

As with tirzepatide, the lipidated 39-residue structure requires a well-chosen HPLC method to resolve closely related impurities, and identity is confirmed by mass spectrometry against the theoretical mass of the fully modified peptide. Regent Peptides supplies retatrutide in six vial strengths, UK manufactured, with each batch tested by Janoshik Analytical and documented against its batch reference.

Retatrutide is an investigational compound. The research-grade peptide supplied here is not a medicine and is supplied solely for in-vitro laboratory research. It is not for human use.