What it is
CagriSema is a combination, not a single molecule. It is two peptides given together under the skin once a week, each at 2.4 mg:
- Cagrilintide — a long-acting analogue of amylin, the 37-residue hormone the pancreas releases alongside insulin. Its formula is C194H312N54O59S2, mass 4,409 Da (PubChem CID 171397054); a fatty side chain lets it bind albumin and last a week.
- Semaglutide — the GLP-1 analogue sold as Wegovy and Ozempic: 31 residues, a fatty acid attached, the same once-weekly design.
The name is the two words run together. Both peptides come from Novo Nordisk, which ran and funded the trials.
How it works
The two parts act on two different hormone systems. GLP-1 comes from the gut after a meal; its receptors in the brain and pancreas lower appetite, slow stomach emptying and raise insulin when glucose is high. Amylin comes from the pancreas's beta cells with insulin and also slows stomach emptying and signals fullness, through its own receptors in the brainstem. The combination tests whether acting on both at once adds up. REDEFINE 1 was designed to answer that with semaglutide-only and cagrilintide-only arms beside the combination and placebo; the abstract reports the combination against placebo only.
What the REDEFINE trials show
Two phase 3a trials, both 68 weeks, both published in the New England Journal of Medicine in 2025:
| REDEFINE 1 (no diabetes) | REDEFINE 2 (type 2 diabetes) | |
|---|---|---|
| Participants | 3,417 (2,108 on the combination) | 1,206 (904 on the combination) |
| Entry | BMI 30+, or 27+ with a complication | BMI 27+, HbA1c 7–10% |
| Mean weight change | −20.4% vs −3.0% placebo | −13.7% vs −3.4% placebo |
| Difference | 17.3 points (95% CI 16.6–18.1) | 10.4 points (95% CI 9.5–11.2) |
| GI adverse events | 79.6% vs 39.9% | 72.5% vs 34.4% |
| Source | PMID 40544433 | PMID 40544432, NCT05394519 |
In REDEFINE 2, 73.5% on the combination reached an HbA1c of 6.5% or less, against 15.9% on placebo. Both trials used a treatment-policy estimand — participants counted in their assigned group whether or not they stayed on the drug — and both added a lifestyle programme in every arm.
What they did not test: neither trial measured heart attacks, strokes or deaths as outcomes, and 68 weeks says nothing about what happens to weight after stopping. A secondary analysis of REDEFINE 1 reports blood-pressure changes (Hypertension, 2026), which is a measurement, not a cardiovascular outcome.
Safety
The published side-effect profile is the GLP-1 class's, larger: gastrointestinal events in roughly three in four treated participants against about one in three on placebo, "mainly transient and mild-to-moderate" (REDEFINE 1). The trials excluded people with a range of conditions, and an investigational combination has no label; whether it suits any individual is a question for a clinician.
Where it stands
- Not approved. openFDA's Drugs@FDA data held no application for cagrilintide on 2026-10-22. Semaglutide alone is approved; cagrilintide alone is not.
- Research record: PubMed indexes 120 records for CagriSema or cagrilintide with semaglutide, 14 tagged as randomised controlled trials; ClinicalTrials.gov lists 31 studies matching "CagriSema" (2026-10-22).
- Read as a weight-loss treatment rather than as a molecule, it is covered on GLP1Ledger's CagriSema page.
Related reading
Each half has its own entry: cagrilintide, the amylin analogue, and semaglutide. The hormone cagrilintide copies is amylin; a third-generation drug that adds glucagon and GIP to GLP-1 is retatrutide.