The TRIUMPH-3 topline data dropped today and the numbers are staggering. Eli Lilly is reporting 24.2% mean body-weight reduction at 48 weeks in participants with obesity (BMI ≥30) on the highest dose arm.
"In TRIUMPH-3, adults with obesity treated with retatrutide achieved a mean body-weight reduction of 24.2% at 48 weeks compared with 2.2% for placebo."
— Eli Lilly press release, 2025
For context, tirzepatide topped out around 22.5% in SURMOUNT-1 at 72 weeks. Retatrutide is hitting harder numbers in fewer weeks. The triple agonist mechanism (GLP-1/GIP/glucagon) seems to be living up to the hype from the Phase 2 data published in NEJM.[1]
Key points from the release:
- Dose-dependent response across all arms
- GI tolerability broadly in line with the class (nausea, vomiting, diarrhea)
- No new safety signals beyond what was seen in Phase 2
- Lilly plans to file with the FDA in 2026
Thoughts? Are we looking at the next standard of care?
[1] Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity. N Engl J Med. 2023;389(6):514-526.
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.
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Shop Reference StandardsI compiled the cross-trial comparison (with the usual caveats about indirect comparisons across different populations):
| Drug | Trial | Peak Weight Loss | Duration |
|---|---|---|---|
| Semaglutide 2.4mg | STEP 1 | 14.9% | 68 wks |
| Tirzepatide 15mg | SURMOUNT-1 | 22.5% | 72 wks |
| Retatrutide 12mg | Phase 2 | 24.2% | 48 wks |
| Retatrutide (P3) | TRIUMPH-3 | ~24% | 48 wks |
| CagriSema | REDEFINE-2 | 22.7% | 68 wks |
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:
- These are mean results. Individual responses will vary substantially — some participants likely lost 30%+, others much less.
- Phase 3 confirmatory data is encouraging but we still need the full publication to assess safety, tolerability breakdown by dose, and subgroup analyses.
- 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.