Retatrutide

Triple agonist (GLP-1 + GIP + glucagon) in late-stage trials — strongest weight loss in development.

Retatrutide adds a third target — glucagon — on top of GLP-1 and GIP. That glucagon arm directly raises energy expenditure and pushes the liver to burn fat, so it doesn't just curb appetite, it turns up the metabolic burn. The result is the largest weight loss seen in any obesity-drug trial to date: ~24% in Phase 2, and up to ~28.7% at the top dose in the Phase 3 TRIUMPH program — territory that rivals bariatric surgery. It's still investigational (no approval yet; a filing is expected late 2026), and the glucagon mechanism is exactly what drives its distinctive risks below.