Retatrutide vs Tirzepatide

Both are single-chain peptides engineered from the GIP backbone with a fatty-acid side chain for once-weekly exposure. Tirzepatide activates the GIP and GLP-1 receptors, reducing appetite and improving insulin secretion.

Retatrutide also activates the glucagon receptor. In research models, glucagon signalling raises energy expenditure and liver fat oxidation, which is the proposed reason for the additional weight and liver-fat effects.

SURMOUNT-1 (2,539 adults without diabetes) reported mean weight reductions of roughly 15–21% across arms at 72 weeks versus about 3% with placebo.

The retatrutide phase 2 obesity trial (338 adults) reported up to 24.2% mean weight reduction at 48 weeks, and a substudy reported large relative reductions in liver fat. These are separate trials with different lengths and populations, so they are not a direct head-to-head.

Both trials reported mostly gastrointestinal events (nausea, diarrhoea, vomiting, constipation), concentrated during dose escalation and mostly mild to moderate.

Retatrutide trials also reported dose-related increases in heart rate that peaked and then declined. Class-wide monitoring considerations include gallbladder events and pancreatitis.

Tirzepatide is approved for type 2 diabetes and chronic weight management, with outcome data in sleep apnoea. Retatrutide is not approved anywhere; its phase 3 TRIUMPH program is in progress.