CagriSema vs Retatrutide
A neutral, side-by-side comparison of two glp-1 & metabolic peptides — their mechanisms, dosing ranges, administration routes, side effects, and research evidence. For research and educational purposes only.
CagriSema
CagriSema is Novo Nordisk's investigational fixed combination of cagrilintide (a long-acting amylin analog) and semaglutide (a GLP-1 receptor agonist). By pairing two complementary appetite pathways, it produced roughly 20–23% weight loss in trials. It was filed with the FDA in December 2025 but is not yet approved — and notably missed non-inferiority against tirzepatide in a head-to-head study.
Full profileRetatrutide
Retatrutide (LY3437943) is Eli Lilly's investigational once-weekly triple agonist of the GIP, GLP-1, and glucagon receptors. Phase 2 data showed 24.2% mean weight loss at 48 weeks; the Phase 3 TRIUMPH program has since reported topline weight loss approaching 28–30% — among the largest reductions recorded for any obesity pharmacotherapy. It is not yet FDA-approved.
Full profile| CagriSema | Retatrutide | |
|---|---|---|
| Category | GLP-1 & Metabolic | GLP-1 & Metabolic |
| Also known as | Cagrilintide + Semaglutide, AM833 + semaglutide, amylin/GLP-1 combination | LY3437943, Triple G, GIP/GLP-1/Glucagon Receptor Agonist |
| Evidence | Investigational (in trials) | Investigational (in trials) |
| Dosing range | 0.25mg–2.4mg mg, once weekly subcutaneous (each component 2.4mg at target) | 2mg–12mg mg, once weekly |
| Administration | Subcutaneous injection (weekly) | Subcutaneous injection (weekly) |
| Key side effects | Nausea (most common, dose-dependent), Vomiting, Diarrhea or constipation, Decreased appetite | Nausea (most common, dose-dependent), Vomiting, Diarrhea, Constipation |
| Cited sources | 2 references | 6 references |
Key differences
- Frequency: CagriSema is typically once weekly subcutaneous (each component 2.4mg at target); Retatrutide is once weekly.
- Research depth: this profile cites 2 sources for CagriSema vs 6 for Retatrutide.
How each works
CagriSema
CagriSema combines amylin-receptor agonism (cagrilintide — satiety and gastric emptying via the area postrema/hypothalamus) with GLP-1 agonism (semaglutide), two non-overlapping appetite mechanisms. The REDEFINE 1 and 2 trials supported a December 2025 FDA filing for weight management. However, the open-label REDEFINE-4 head-to-head trial showed 23.0% weight loss vs 25.5% for tirzepatide 15 mg, missing its primary non-inferiority endpoint. An FDA decision is expected in late 2026.
Retatrutide
Across the Phase 2 trial (NEJM 2023, Jastreboff et al.) and the Phase 3 TRIUMPH registrational program (TRIUMPH-1 through -4), retatrutide has produced dose-dependent weight loss reaching ~28.3% at 80 weeks (TRIUMPH-1, 12 mg) and ~28.7% at 68 weeks in a knee-osteoarthritis population (TRIUMPH-4, 12 mg), alongside improvements in glycemia, blood pressure, lipids, and liver fat. The glucagon component is thought to add energy expenditure on top of the appetite suppression driven by GLP-1 and GIP. As of mid-2026, Phase 3 efficacy figures are topline (press-release/conference level) and not yet published in full peer-reviewed form.
This comparison aggregates public research and structured profile data for informational purposes only. It is not medical advice and does not recommend either compound for human use. Consult a qualified healthcare provider before considering any peptide.