Retatrutide vs Semaglutide

A triple agonist of GIP, GLP-1, and glucagon receptors in late-stage clinical trials, producing ~24% weight loss at 48 weeks in Phase 2 — the largest effect size of any weight-loss pharmaceutical to date.

A GLP-1 receptor agonist originally approved for type 2 diabetes and now widely used for chronic weight management, producing 15%+ reductions in body weight over 12 months in clinical trials.

Retatrutide simultaneously activates three incretin/metabolic receptors. The addition of glucagon agonism is thought to increase energy expenditure, complementing the appetite suppression driven by GIP and GLP-1.

Semaglutide mimics the incretin hormone GLP-1, slowing gastric emptying, reducing appetite via hypothalamic signalling, and enhancing glucose-dependent insulin secretion. The result is sustained calorie reduction without conscious restriction.

Phase 2 used 1–12 mg weekly; optimal dose pending Phase 3

0.25 mg weekly, titrated up to 2.4 mg weekly for weight loss

~6 days

~7 days

Subcutaneous once weekly

Subcutaneous once weekly, Oral (lower bioavailability)

investigational

approved

Not yet listed

Not yet listed