CagriSema (Cagrilintide + Semaglutide Combination) — Weight & Metabolism
Fixed-dose combination of cagrilintide (amylin analog) and semaglutide (GLP-1 agonist) in Phase 3 trials for obesity.
Overview
CagriSema is Novo Nordisk's investigational fixed-ratio combination of cagrilintide (a long-acting amylin analog) and semaglutide (a GLP-1 receptor agonist) in a single once-weekly subcutaneous injection. By targeting two distinct hormonal pathways that regulate appetite and metabolism, CagriSema aims to achieve superior weight loss compared to either component alone. Amylin, a peptide co-secreted with insulin from pancreatic beta cells, acts on the area postrema and hypothalamus to promote satiety, slow gastric emptying, and suppress glucagon. Cagrilintide is an acylated amylin analog with an extended half-life suitable for weekly dosing. In Phase 2 trials, CagriSema demonstrated weight loss of approximately 15.6% at 32 weeks, with some cohorts approaching 17%, and was generally well tolerated. The REDEFINE Phase 3 program is evaluating CagriSema across multiple obesity and T2DM populations, with initial results reported in 2024-2025. Novo Nordisk positions CagriSema as a potential best-in-class obesity treatment, leveraging their expertise with semaglutide (Ozempic/Wegovy) and combining it with the complementary amylin pathway.
Indications
- Investigational: Chronic weight management in obesity (Phase 3)
- Investigational: Type 2 diabetes with obesity (Phase 3)
- Investigational: Cardiovascular risk reduction in obesity (planned)
Mechanism of Action
Activates hypothalamic GLP-1 receptors to reduce appetite and food intake; enhances glucose-dependent insulin secretion
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| CagriSema (cagrilintide/semaglutide) | Titration doses | Once weekly | Fixed-ratio combination; dose escalation over 16 weeks |
| CagriSema | 2.4 mg cagrilintide / 2.4 mg semaglutide | Once weekly | Target maintenance dose from Phase 3 trials |
Evidence Grade
GRADE B
Safety & Contraindications
- GI side effects: nausea, vomiting, diarrhea — consistent with GLP-1/amylin class
- Injection site reactions (erythema, pruritus)
- Dose-dependent tolerability — requires titration schedule
- Potential for hypoglycemia when combined with insulin or sulfonylureas
- Cholelithiasis risk with rapid weight loss
- Not yet approved — limited long-term safety data
- Pancreatitis risk (rare, class effect of GLP-1 agonists)