Retatrutide

A first-in-class triple receptor agonist that simultaneously activates GIP (glucose-dependent insulinotropic polypeptide), GLP-1 (glucagon-like peptide-1), and glucagon receptors. The triple mechanism creates a uniquely comprehensive metabolic effect: GLP-1 activation suppresses appetite and improves insulin sensitivity; GIP activation enhances the GLP-1 effect and may directly promote fat cell lipolysis; glucagon receptor activation increases energy expenditure and hepatic fat reduction — an effect not achieved by semaglutide (GLP-1 only) or tirzepatide (GLP-1/GIP). The glucagon component specifically addresses visceral fat and liver fat in ways that dual agonists cannot, making retatrutide particularly promising for metabolic-associated fatty liver disease (MAFLD).

Developed by Eli Lilly. The pivotal Phase 2 SURMOUNT-4 trial published in the New England Journal of Medicine showed average body weight reduction of 24.2% at 48 weeks — the highest weight loss ever recorded in a pharmaceutical obesity trial, surpassing tirzepatide (22.5% in SURMOUNT-1) and semaglutide (14.9% in STEP 1). Phase 2 data also demonstrated significant improvements in liver fat content (MAFLD marker), lipid profiles, and blood pressure. Phase 3 trials are active as of 2026, with potential TGA/FDA approval in 2027 if trials succeed. Currently generating the highest search interest of any emerging peptide globally. ProtocolHub will update this profile when Australian regulatory status changes.

Ongoing — minimum 48 weeks per Phase 2 protocol