CagriSema (Cagrilintide + Semaglutide) Combination Therapy — Weight & Metabolism
Investigational fixed-dose combination of cagrilintide (amylin analog) and semaglutide (GLP-1 RA) for superior weight loss through dual pathway activation.
Overview
CagriSema is a fixed-dose combination of cagrilintide 2.4mg (a long-acting amylin receptor agonist) and semaglutide 2.4mg (a GLP-1 receptor agonist) developed by Novo Nordisk, currently in Phase 3 trials (REDEFINE program). Phase 2 data (n=92, 32 weeks) demonstrated approximately 15.6% mean body weight loss, significantly superior to semaglutide 2.4mg alone (5.1%) at the same timepoint. The combination targets two complementary satiety pathways: amylin receptors in the area postrema/hindbrain and GLP-1 receptors in the hypothalamus, providing additive appetite suppression beyond what either agent achieves alone. Phase 3 REDEFINE-1 trial results showed 20.4% weight loss at 68 weeks in people with obesity, with 60% of participants achieving >=20% weight loss and 23% achieving >=30% weight loss. REDEFINE-2 (T2DM) showed 15.7% weight loss and 74% achieved HbA1c <=6.5%. Regulatory submission anticipated 2025-2026. PMID: 37385275, 38587564.
Indications
- Obesity (BMI >=30) or overweight (BMI >=27) with weight-related comorbidities (Phase 3)
- Type 2 diabetes with obesity requiring maximum weight loss and glycemic control (Phase 3)
- Patients who have plateaued on GLP-1 RA monotherapy seeking additional weight loss
Mechanism of Action
Impaired amylin and GLP-1 signaling leads to inadequate appetite suppression and metabolic dysregulation
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| CagriSema (Cagrilintide + Semaglutide) | Escalating doses | Once weekly | 16-week titration of both components to target doses; reduces GI side effects |
| CagriSema | Cagrilintide 2.4 mg + Semaglutide 2.4 mg | Once weekly (single injection) | Full maintenance dose; 20.4% weight loss at 68 weeks in Phase 3 |
Evidence Grade
GRADE B
Safety & Contraindications
- Investigational fixed-dose combination - NOT FDA-approved; Phase 3 trials ongoing
- GI side effects expected from both components: nausea, vomiting, diarrhea, constipation
- Gradual titration over 16 weeks is critical to minimize GI adverse events
- Lower discontinuation rates than expected given dual mechanism (amylin pathway better tolerated)
- Long-term safety data (>68 weeks) being established in ongoing REDEFINE trials
- Potential for interactions with medications affected by delayed gastric emptying