CagriSema — Cagrilintide + Semaglutide Blend Dosage Protocol
CagriSema is Novo Nordisk's investigational combination of cagrilintide (amylin analog) and semaglutide (GLP-1 agonist) under Phase 3 evaluation. The dual mechanism — amylin receptor satiety + GLP-1 receptor appetite suppression — produces greater weight loss than either agent alone in Phase 2 trials.
⚡ Quickstart Highlights
Dosing & Reconstitution Guide
Route: Subcutaneous | Frequency: Both compounds once weekly on the same day, separate injections
| Compound | Weekly Dose | Notes |
|---|---|---|
| Semaglutide (follow titration ladder) | 0.25 → 2.4 mg | See Semaglutide protocol for full titration |
| Cagrilintide (follow titration ladder) | 0.3 → 2.4 mg | See Cagrilintide protocol for full titration |
See the Semaglutide Protocol and Cagrilintide Protocol for full individual reconstitution instructions, titration ladders, and supply calculations.
Supplies Planning
| Item | 16 Weeks | 28 Weeks |
|---|---|---|
| Semaglutide vials (5 mg) | 4 vials | 7 vials |
| Cagrilintide vials (5 mg) | 4 vials | 7 vials |
| Insulin syringes (U-100) | 32 | 56 |
| BAC water (10 mL) | 2–4 × 10 mL | 4–6 × 10 mL |
Mechanism of Action
CagriSema combines complementary satiety mechanisms operating through different receptor pathways. Semaglutide activates GLP-1 receptors in the hypothalamus, brainstem, and vagal afferents to reduce appetite, slow gastric emptying, and improve insulin sensitivity. Cagrilintide activates amylin receptors (CTRs/RAMPs complexes) in the area postrema and nucleus tractus solitarius, adding complementary satiety signaling, post-meal glucagon suppression, and additional gastric motility effects.
The dual-pathway mechanism appears additive rather than redundant. Phase 2 CAGRISEMA data demonstrated approximately 15.6% weight loss at 32 weeks — exceeding semaglutide 2.4 mg monotherapy (~10–14%) at matched timepoints, supporting the combination hypothesis.
Research Findings & Safety Profile
- Phase 2 CAGRISEMA trial: 15.6% weight loss at 32 weeks vs 5.1% placebo — exceeding semaglutide monotherapy.
- Phase 3 REDEFINE 1 and REDEFINE 2 trials ongoing as of 2025.
- Dual amylin + GLP-1 receptor mechanisms appear additive, not redundant.
- Adverse effect profile overlapping with semaglutide monotherapy: nausea, vomiting, diarrhea — slightly higher incidence with combination.
- Both compounds have ~7-day half-lives — stable weekly steady-state achieved after 4–5 weeks.
- Not yet FDA approved; investigational.
Storage
| State | Temperature | Duration | Notes |
|---|---|---|---|
| Lyophilized | −20°C (−4°F) | Up to 24 months | Dry, dark conditions |
| Reconstituted | 2–8°C (35–46°F) | Up to 28 days | Avoid freeze-thaw; protect from light |