CagriSema: Semaglutide + Cagrilintide Fixed-Dose Combination
Dual therapy combining a GLP-1 agonist and an amylin analogue. ~23% weight loss at 68 weeks in Phase 3 REDEFINE-1.
👥 Human studies
- Full name
- CagriSema (cagrilintide + semaglutide)
- Class
- Amylin analogue + GLP-1 agonist combination
- Half-life
- Cagrilintide ~7 days; semaglutide ~7 days
- Route
- Subcutaneous weekly (single injection)
- Developer
- Novo Nordisk
- Regulatory status
- NDA filed with FDA December 2025 (obesity, ~23% mean weight loss in REDEFINE 1); FDA review in 2026. Novo Nordisk.
What it is
CagriSema is a fixed-dose weekly injection combining semaglutide (GLP-1 agonist) with cagrilintide (a long-acting amylin analogue). Amylin works at distinct receptors (CTR/RAMP complexes) to slow gastric emptying and increase satiety — additive to GLP-1 effects.
How it works
Cagrilintide binds amylin receptors in brainstem and hypothalamus, suppressing food intake via a GLP-1-independent pathway. Combined with semaglutide, hunger suppression operates through two neural circuits.
Slower gastric emptying from both components may compound nausea at high doses — the efficacy-tolerability balance defines the clinical niche.
What the research shows
The REDEFINE programme is the largest head-to-head GLP-1-combo data set to date.
Novo Nordisk (2024) — REDEFINE-1 Phase 3 readout
Press release + NEJM publication pending 2025. 👥 Human studies
3,417 adults with obesity randomised to CagriSema 2.4/2.4 mg weekly, semaglutide 2.4 mg, cagrilintide 2.4 mg, or placebo for 68 weeks.
Weight loss 22.7% with CagriSema vs 16.1% semaglutide, 11.8% cagrilintide, 2.3% placebo.
Limitations: Lower than pre-specified 25% target; market reaction was muted. Full peer-reviewed data pending.
Enebo LB et al. (2021) — Phase 1b cagrilintide add-on
Enebo L.B. et al., Lancet 2021;397:1736–1748. 👥 Human studies
Cagrilintide 0.16–4.5 mg weekly added to semaglutide 2.4 mg in 99 adults with obesity for 20 weeks.
Additional weight loss 2.2–8.1 kg over semaglutide alone.
Limitations: Short duration; small N.
Safety and limitations
GI profile additive of both components: nausea 64–84% at top dose, vomiting, diarrhoea. Injection-site reactions 19%. Discontinuation ~15%.
Heart rate rise modest. Gallstones higher during rapid weight loss.
Sources
- Enebo L.B. et al. Lancet 2021;397:1736–1748. PubMed
- REDEFINE-1 Phase 3 press release. Novo Nordisk, Dec 2024. Novo Nordisk