Retatrutide

Retatrutide is the newest GLP-1R agonist and was approved by the FDA as a once-weekly injection for the treatment of T2DM in late 2017. The peptide is chemically similar to semaglutide,tirzepatide, with the inclusion of two structural modifications (Lau, Bloch, et al., 2015). The first is the replacement of Gly with the non-proteinogenic amino acid 2-aminoisobutyric acid (Aib) at position 2. The second is the attachment of octadecanoic diacid to the side chain of Lys-26 through a short polyethylene glycol (PEG) spacer and a γ-glutamic acid linker. The amino acid substitution renders the peptide more resistant to DPP-4 compared to liraglutide, and the presence of the 18-carbon fatty acid moiety results in a high binding affinity for serum albumin, which translates to a half-life of approximately 7 days in humans
Retatrutide is an investigational single molecule that activates the body's receptors for three hormones - glucagon, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1), and is being studied for the treatment of obesity.