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The next weight-loss arms race is Lilly's triple agonist against Novo's amylin combo. One posted the deepest trial weight loss ever seen in the class; the other is already sitting at the FDA. Here is how the two next-gen drugs actually compare — and the honest caveat that neither is available yet.
| Retatrutide | CagriSema | |
|---|---|---|
| Maker | Eli Lilly | Novo Nordisk |
| Mechanism | Triple agonist: GLP-1 + GIP + glucagon | Amylin analog (cagrilintide) + semaglutide |
| Weight loss | ~28.3% at 80 wk (up to 30.3%) | ~22.7% at 68 wk |
| Pivotal trial | TRIUMPH-1 (Phase 3, topline May 2026) | REDEFINE-1 (Phase 3) |
| Regulatory status | Phase 3; NDA expected late 2026 | NDA filed Dec 18, 2025 |
| Likely availability | ~2027 | 2026 at earliest (unconfirmed) |
| Extra target | Liver fat / MASH (glucagon arm) | New amylin satiety pathway |
Retatrutide’s Phase 3 TRIUMPH-1 topline (May 2026) reported ~28.3% mean weight loss at 80 weeks on the 12 mg dose — up to 30.3% in higher-BMI cohorts, with 45% of patients losing ≥30%of their body weight. That is roughly a 7-point edge over tirzepatide (Zepbound, ~21%) and the deepest loss any GLP-1-class molecule has shown. CagriSema’s REDEFINE-1 reached ~22.7% at 68 weeks — category-leading, though it landed below the ~25% Novo had guided, which cooled expectations. Both tower over diet-alone results; see the full field in the GLP-1 comparison chart.
The drugs get there differently. Retatrutide is a single molecule hitting three receptors — GLP-1, GIP, and glucagon; the glucagon arm adds energy expenditure and mobilizes liver fat, which is why it is also being studied for fatty-liver disease (MASH). CagriSema pairs cagrilintide, a long-acting amylin analog, with semaglutide — layering a second, genuinely new satiety pathway on top of GLP-1. To understand the receptor language, see what a GLP-1 is.
Efficacy favors retatrutide; availability favors CagriSema. Novo filed CagriSema with the FDA on December 18, 2025, with review during 2026 (no decision date public yet). Retatrutide only reached Phase 3 topline in May 2026, so an FDA filing is expected late 2026 and approval likely 2027, pending the rest of the TRIUMPH program. Track both on the GLP-1 pipeline tracker.
Neither drug is available outside clinical trials, and the earliest realistic timelines are 2026–2027. Do not delay treatment waiting for them. The approved drugs already work: tirzepatide (Zepbound) averages ~21% and semaglutide (Wegovy) ~15%. Start with what is available now — compare them in Wegovy vs Zepbound — and revisit a next-gen option if and when it is approved and right for you.