Glucagon-mediated thermogenesis on retatrutide — need advice

I've been following the TRIUMPH program since the Phase 2 readout and honestly, these numbers are consistent with what we already saw. The Phase 2 dose-finding study showed up to 24.2% weight loss at 48 weeks with the 12 mg dose. The fact that Phase 3 is confirming that with a larger cohort is extremely encouraging.

What I want to see is the body composition data. If the glucagon component is genuinely increasing energy expenditure and promoting fat oxidation while the GIP component helps preserve lean mass, that's a fundamentally different metabolic profile than pure GLP-1 agonism.

Also keeping my eye on the TRIUMPH-2 readout for T2D. If the A1C reduction is in the 2.0%+ range alongside this kind of weight loss, it's going to be very difficult for payors to justify restricting access.

24% in 48 weeks is absolutely wild. I'm currently on tirzepatide and have lost about 18% in 40 weeks. The idea that a next-gen drug could do even more is exciting but also raises questions about diminishing returns. At some point you're losing weight faster than your body can adapt — loose skin, gallstones, nutritional deficiencies.

Did the press release mention anything about lean mass preservation? That's my biggest concern with any aggressive weight loss.

I compiled the cross-trial comparison (with the usual caveats about indirect comparisons across different populations):

Note the timeframe difference. Retatrutide is achieving comparable or superior weight loss in significantly less time. Whether the curve plateaus or continues trending down with extended treatment will be crucial data from the open-label extensions.

Great discussion, everyone. A few reminders:

1. These are mean results. Individual responses will vary substantially — some participants likely lost 30%+, others much less.
2. Phase 3 confirmatory data is encouraging but we still need the full publication to assess safety, tolerability breakdown by dose, and subgroup analyses.
3. Please don't extrapolate clinical trial results to compounded or research-grade products. The purity, dosing, and medical oversight are not equivalent.

Locking this as a reference thread. New discussion points → new threads please.