Retatrutide vs. tirzepatide: where the trial evidence stands

A starter thread laying out the evidence base for each compound. Corrections and newer data are very welcome, since this area moves fast.

Tirzepatide (GIP/GLP-1 dual agonist)

• It’s approved for type 2 diabetes (Mounjaro) and chronic weight management (Zepbound), and has since gained further indications.
• It’s backed by large phase 3 programs: SURPASS for diabetes and SURMOUNT for obesity. In SURMOUNT-1, mean weight reduction at 72 weeks was roughly 15–21% depending on dose, vs. about 3% on placebo.
• There is now a substantial body of long-term safety data. The most common adverse events are GI effects (nausea, diarrhea, vomiting), mostly during dose escalation.

Retatrutide (GIP/GLP-1/glucagon triple agonist)

• It’s investigational and not approved anywhere.
• The phase 2 obesity trial (published in NEJM in 2023) reported mean weight reduction of up to about 24% at 48 weeks at the highest dose.
• The phase 3 TRIUMPH program is underway. Check the latest company releases and publications for readouts.
• The glucagon-receptor component is thought to increase energy expenditure and affect liver fat, which is an active research interest. Its effects on heart rate and other safety signals are being watched in phase 3.

Comparing them fairly

• Cross-trial comparisons are shaky. Populations, durations, and dose-escalation schemes differ. Only a head-to-head trial gives a clean comparison.
• Phase 2 results often shrink somewhat in larger phase 3 populations.
• As the forum description notes, research-grade material is not the same product as the approved pharmaceutical and isn’t interchangeable with it.

Share trial readouts and papers below as they come out.