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CagriSema and retatrutide are the two most-watched next-generation obesity candidates, and they represent opposite bets. Novo Nordisk combines two existing peptides (amylin plus GLP-1); Eli Lilly engineers a single molecule that hits three receptors (GIP, GLP-1, and glucagon). Both are investigational, and their reported numbers sit at the top of the field.
Research reference only. Not medical advice, prescribing guidance, or a product recommendation.
| Dimension | CagriSema | Retatrutide |
|---|---|---|
| Strategy | Combine two peptides | One molecule, three receptors |
| Mechanism | Amylin (cagrilintide) + GLP-1 (semaglutide) | GIP + GLP-1 + glucagon |
| Developer | Novo Nordisk | Eli Lilly (LY3437943) |
| Peak weight ↓ (trial) | ~20.4% (REDEFINE 1, 68 wk; up to 22.7% adherence) | ~24% (Phase 2, 48 wk, 12 mg) |
| Extra vs GLP-1 | Amylin — a separate satiety pathway | GIP (insulinotropic) + glucagon (energy expenditure, liver fat) |
| Approval status | Investigational (Phase 3 REDEFINE) | Investigational (Phase 3 TRIUMPH) |
| Molecular identity | No single formula — a co-formulation | Single peptide, MW 4731.5 |
| Maturity of evidence | Phase 3 reporting | Phase 2 complete; Phase 3 ongoing |
−20.4% vs −3.0% (placebo)
Mean body-weight change (obesity) · n=3417 · 68 wk — Beat semaglutide (−14.9%) and cagrilintide (−11.5%) alone
~24% vs ~2% (placebo)
Mean body-weight change · n=338 · 48 wk — Jastreboff et al., NEJM 2023; highest-dose arm
Reporting — neither FDA-approved
Confirmatory efficacy/safety · Ongoing — Head-to-head trials between them have not been run
On the numbers reported so far, retatrutide’s ~24% (Phase 2, 48 weeks) edges CagriSema’s ~20.4% (Phase 3, 68 weeks) — but these are different trials at different stages, not a head-to-head, so the gap is suggestive at best. The more durable distinction is strategic: a two-peptide combination that can be built from proven parts versus a single triple-agonist molecule that adds glucagon-driven energy expenditure and liver-fat effects GLP-1/amylin do not. Both are investigational; neither is approved. Treat this as mechanism plus early data, not a ranking.
CagriSema is a combination of two peptides — cagrilintide (amylin) and semaglutide (GLP-1). Retatrutide is a single molecule that activates three receptors — GIP, GLP-1, and glucagon. CagriSema adds a separate satiety pathway (amylin); retatrutide adds insulinotropic (GIP) and energy-expenditure/liver-fat (glucagon) mechanisms.
Reported figures put retatrutide at ~24% (Phase 2, 48 weeks) and CagriSema at ~20.4% (Phase 3 REDEFINE 1, 68 weeks). These come from separate trials at different stages, not a direct comparison, and retatrutide’s Phase 3 results are still pending — so it is premature to rank them.
No. Both are investigational and in Phase 3 — CagriSema in Novo Nordisk’s REDEFINE program, retatrutide in Eli Lilly’s TRIUMPH program. Neither is FDA-approved.
Glucagon-receptor agonism is studied for increased energy expenditure and hepatic (liver) fat reduction — effects that neither GLP-1 nor amylin provide directly. CagriSema’s advantage is being buildable from two already well-characterized peptides. This page is a research and educational reference.
Mechanism, evidence, and trade-offs between CagriSema and Retatrutide — citation-backed answers grounded in PubMed, PubChem, and ClinicalTrials.gov.