Comparison
Compound Receptors Status Best published weight loss
Semaglutide GLP-1 Approved ~15% at 68 weeks (STEP 1)
Tirzepatide GIP + GLP-1 Approved ~21% at 72 weeks (SURMOUNT-1)
Retatrutide GIP + GLP-1 + glucagon Investigational 24.2% at 48 weeks (Phase II)
A caveat almost every comparison mentions
There has not yet been a randomized controlled trial directly comparing retatrutide with semaglutide or tirzepatide. All claims that “retatrutide is better than tirzepatide” come from placing data from different trials side by side, and those trials differ in participants, duration, and endpoints.
Network meta-analysis
The closest thing to a fair comparison is a 2025 network meta-analysis pooling 19 trials and 29,506 adults. It showed that retatrutide had the highest odds of achieving 15% weight loss, but also the highest adverse event risk among all drugs. These two conclusions are linked, and anyone citing only the first without mentioning the second is selling something.
Approval status differences
Semaglutide and tirzepatide are approved in multiple countries for weight loss and diabetes. Retatrutide has not been approved in any country, and Lilly plans to file with the FDA in Q1 2027.
Conclusion
The three differ in mechanism, data, and approval status. The absence of head-to-head trials means all cross-drug comparisons should be treated with caution.