CagriSema — a fixed once-weekly combination of the amylin analog cagrilintide and the GLP-1 agonist semaglutide, both at 2.4 mg — is investigational. Its phase 3 program (REDEFINE) has published results, but it is not an approved product, and compounded or research-grade "CagriSema" is not the trial drug.
Overview
The benefit CagriSema has demonstrated is large-scale weight loss: in its pivotal phase 3 trial, adults with obesity lost an average of 20.4% of body weight over 68 weeks, versus 3.0% on placebo — among the largest reductions ever recorded for a medication in a phase 3 obesity trial. The design idea is simple: pair semaglutide's GLP-1 signaling with cagrilintide's amylin signaling so two distinct appetite pathways work at once. The published data now span a phase 1b study, a phase 2 diabetes trial, and the phase 3 REDEFINE program.
REDEFINE 1 — the headline trial
REDEFINE 1 randomized 3,417 adults with obesity (or overweight plus a weight-related condition) but no diabetes to CagriSema, either component alone, or placebo for 68 weeks (NEJM 2025):
- −20.4% mean weight change on CagriSema vs −3.0% on placebo — a 17.3-percentage-point treatment difference.
- Significantly more participants on the combination cleared the 20%, 25%, and even 30% weight-loss thresholds than on placebo.
- The combination out-performed both monotherapy arms, supporting the claim that the pairing itself — not just the semaglutide inside it — does the work.
For scale: semaglutide 2.4 mg alone produced about 14.9% weight loss in its own pivotal trial, so the combination moved the class benchmark by roughly five percentage points.
The type 2 diabetes data
A 32-week phase 2 trial in 92 people with type 2 diabetes compared CagriSema against each component alone, all escalated to 2.4 mg weekly (Lancet 2023). CagriSema reduced HbA1c by 2.2 percentage points (vs 1.8 for semaglutide and 0.9 for cagrilintide) and body weight by 15.6%, versus 5.1% with semaglutide and 8.1% with cagrilintide alone — a threefold weight advantage over semaglutide monotherapy in this population. People with diabetes typically lose less weight on GLP-1 drugs than people without it, which makes the combination's margin here especially notable.
Why two mechanisms beat one
Semaglutide works through GLP-1 receptors — boosting glucose-dependent insulin release, slowing gastric emptying, damping appetite via the brain. Cagrilintide is an analog of amylin, the pancreatic hormone that signals meal-ending satiety largely through hindbrain circuits. The pathways are parallel rather than redundant, so their effects add: the earliest co-administration study already showed up to 17.1% weight loss at 20 weeks versus 9.8% for semaglutide plus placebo — in healthy volunteers, before any phase 3 machinery existed (Lancet 2021). The same additivity applies to side effects — both mechanisms slow the gut — which is covered on the side-effects page.
The caveats
- CagriSema is not approved; regulatory review follows the REDEFINE program, and availability claims by vendors are false by definition.
- Averages hide spread — individual responses in REDEFINE 1 ranged widely, and trial results came with structured titration and support.
- Benefits are conditional on continuing treatment, as with every agent in this class.
- All data describe the verified fixed-dose product; two loose vials of "cagrilintide" and "semaglutide" from a gray-market source are not CagriSema.