Retatrutide

Where Tirzepatide activates two incretin receptors, Retatrutide adds a third: the glucagon receptor. This three-pathway profile engages appetite signalling, insulin response, and energy expenditure simultaneously, producing a broader metabolic effect than dual- or single-agonist compounds. Researchers are particularly interested in the glucagon-receptor contribution, which is thought to increase basal energy expenditure alongside the appetite effects familiar from the incretin class.

Retatrutide has progressed through Phase 1 and Phase 2 and is currently in Phase 3 evaluation, focused on long-term safety, sustained metabolic effects, and hepatic and cardiovascular endpoints. The Phase 2 data drew particular attention for the magnitude of weight reduction observed over 48 weeks.

Retatrutide's published trial data has drawn significant attention:
Body weight: Phase 2 trials reported reductions of approximately 15–24% from baseline depending on dose and duration — among the most pronounced responses ever recorded in this drug class.
Glycaemic control: Improvements in fasting and post-prandial glucose alongside enhanced insulin sensitivity in type 2 diabetes cohorts.
Lipid profile: Reductions in LDL cholesterol and triglycerides.
Hepatic markers: Active investigation in NAFLD and NASH.
Cardiovascular indicators: Secondary endpoints suggesting potential improvements in cardiovascular risk markers, with long-term data still accumulating.