CagriSema
Also known as: Cagrilintide 2.4 mg + Semaglutide 2.4 mg, AM833 + Semaglutide, Cagrilintide/semaglutide fixed-dose combination, First GLP-1/amylin combination injectable
Overview
CagriSema is an investigational fixed-dose combination of two distinct obesity medications in a single once-weekly subcutaneous injection: cagrilintide 2.4 mg (a long-acting amylin analog, slug: cagrilintide) and semaglutide 2.4 mg (a GLP-1 receptor agonist, the same active ingredient as Wegovy, slug: semaglutide), developed by Novo Nordisk. By co-administering an amylin analog with a GLP-1 agonist, CagriSema exploits complementary satiety pathways — amylin acting in the area postrema and GLP-1 acting in the hypothalamus — producing additive weight loss superior to either component alone. The Phase 3 REDEFINE program demonstrated 22.7% mean weight loss at 68 weeks (REDEFINE 1) versus 16.1% for semaglutide monotherapy and 1.8% for placebo. Novo Nordisk filed an NDA with the FDA in December 2025; a decision is expected ~October 2026. If approved, CagriSema would be the first-ever fixed-dose GLP-1/amylin combination product and would compete directly with tirzepatide (Zepbound) and retatrutide.
Mechanism of Action
Fixed-dose GLP-1 + amylin dual agonism: semaglutide activates GLP-1R in hypothalamus and brainstem (appetite suppression, insulin secretion, glucose lowering); cagrilintide activates amylin receptors (AMY1-3) in area postrema and nucleus accumbens (postprandial glucagon suppression, gastric emptying delay, additive satiety). The two pathways are complementary and additive, producing weight loss significantly greater than either agent alone. A single once-weekly SC injection delivers both drugs simultaneously.
Potential Benefits
- REDEFINE 1 (68 weeks, obesity): 22.7% mean weight loss vs. 16.1% semaglutide alone and 1.8% placebo
- REDEFINE 1: 91.9% of CagriSema patients achieved ≥5% weight loss
- REDEFINE 1: ~54% of patients with obesity reached non-obesity BMI (<30) at week 68
- REDEFINE 2 (68 weeks, T2D): 15.7% weight loss vs. 3.1% placebo
- REIMAGINE 2 (68 weeks, T2D): superior HbA1c reduction -1.91% vs. semaglutide -1.76%
- REIMAGINE 2: superior weight loss 14.2% vs. semaglutide 10.2%
- REDEFINE 4 (head-to-head vs. tirzepatide): 20.2% vs. 23.6% weight loss — clinically competitive
- REIMAGINE 2: no weight-loss plateau at 68 weeks; 43% achieved ≥15% weight loss
- REDEFINE 3: step-up from semaglutide to CagriSema produces additional weight loss
- Single injection device combines both drugs — improved convenience vs. separate injections
Research Dosage Notes
The following reflects doses used in published research studies. This is not medical advice.
Consult published research literature for study-specific protocols.
Routes of Administration
Subcutaneous Injection High (both components; semaglutide ~89% SC bioavailability; cagrilintide high SC bioavailability)
Once-weekly SC injection delivering both cagrilintide 2.4 mg and semaglutide 2.4 mg in a single fixed-dose device. Same injection sites as Wegovy: abdomen, thigh, or upper arm.
Read our full Routes of Administration Guide for detailed comparison of all delivery methods.
Stacking Protocols
Popular research stacks involving CagriSema:
Metabolic Health Stack
Combines CagriSema with MOTS-c (mitochondrial metabolism) and AOD-9604 (lipolysis) for metabolic optimization.
Explore our complete Peptide Stacking Guide for more combinations and safety considerations.
Reconstitution
| Storage | Refrigerate at 2-8°C after reconstitution. Do not freeze reconstituted solution. |
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Typical vial sizes: 5 mg. Add bac water slowly down the side of the vial, swirl gently — do not shake. Use insulin syringe for precise dosing.
Need exact syringe measurements?
Amino Acid Sequence
Combination product: Cagrilintide (modified 37 AA amylin sequence, acylated) + Semaglutide (31 AA GLP-1 analog, C18 fatty acid chain, Aib substitution at position 2)
Side Effects & Safety
- Nausea (most common; class effect of both GLP-1 and amylin; typically mild to moderate)
- Vomiting
- Diarrhea
- Constipation
- Decreased appetite (intended therapeutic effect)
- Gastrointestinal adverse events are the most common AEs — diminish over time
- Safety profile consistent with GLP-1 receptor agonist and amylin analog class
- No new safety signals beyond individual component effects
- Standard GLP-1 class warnings apply: thyroid C-cell tumor risk, pancreatitis (rare)
- High completion rates in Phase 3 trials — favorable tolerability
Safety & Contraindications
This information is for educational purposes only. Consult a qualified healthcare provider before using any peptide.
MTC/MEN2
Contains semaglutide (GLP-1 RA). Contraindicated in patients with personal or family history of MTC or MEN2.
Severe Gastroparesis
Dual amylin/GLP-1 mechanism significantly delays gastric emptying. Avoid in severe gastroparesis.
Pancreatitis History
GLP-1 agonists associated with acute pancreatitis. Discontinue if suspected.
Pregnancy & Lactation
Contraindicated in pregnancy. Discontinue semaglutide component at least 2 months before conception.
Drug Interactions
- Insulin/sulfonylureas: Substantial risk of hypoglycemia due to dual mechanism. Proactive dose reduction of insulin recommended.
- Oral medications: Significant delay in gastric emptying may reduce absorption of oral medications. Space administration appropriately.
FDA Safety Information
NDA filed with FDA; PDUFA decision expected October 2026. Combines cagrilintide 2.4mg + semaglutide 2.4mg in fixed-dose combination.
Pharmacokinetics
| Half-Life | ~7 days for both components (cagrilintide: ~7 days; semaglutide: ~7 days) — both enable once-weekly dosing |
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| Storage | Refrigerate at 2–8°C; do not freeze; protect from light; pre-filled auto-injector pen |
Synergistic Compounds
The following compounds have been studied alongside CagriSema for potential complementary or synergistic effects:
Learn More
References & Further Reading
- CoadministeredCagrilintide and semaglutide in adults with overweight or obesity — REDEFINE 1 (NEJM 2025)
- Novo Nordisk files for FDA approval of CagriSema — December 2025 NDA
- ADA 2025: CagriSema demonstrates significant weight loss in REDEFINE clinical trials
- Novo Nordisk's CagriSema outperforms Ozempic in Phase III REIMAGINE 2 trial
- Novo Nordisk's CagriSema bested by Lilly's Zepbound in REDEFINE 4 head-to-head trial