Retatrutide

Potentially the most efficacious obesity compound in development. Phase II weight loss rivaled bariatric surgery outcomes. Phase III trials are ongoing.

A rough internal score reflecting quantity, quality, and consistency of human evidence. Not a clinical recommendation.

Phase II data showed up to 24.2% mean weight loss at the 12 mg dose over 48 weeks. The glucagon receptor component may contribute additional energy expenditure and hepatic fat reduction. Phase III trials are underway for obesity and type 2 diabetes.

• ~24% mean weight loss in Phase II at highest dose
• Triple-receptor mechanism targeting multiple metabolic pathways
• Once-weekly subcutaneous dosing
• Potential hepatic fat reduction via glucagon agonism

Phase II studied 1–12 mg subcutaneously once weekly with dose titration.

• Nausea
• Diarrhea
• Vomiting
• Constipation

Not yet approved. GI side effects are common. Long-term safety of triple agonism, particularly the glucagon component, requires further evaluation.

Phase II results, while striking, involve relatively small sample sizes. Phase III confirmation is needed.

• Weight loss82
• Longevity35