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. |
|---|
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 |
|---|---|
| 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
Latest News & Research
View all articles →
FDA Staff Reviewers Say ‘No’ to 7 Compounded Peptides Ahead of July PCAC Vote
FDA staff reviewers urged against adding seven popular peptides to the 503A bulks list ahead of the July PCAC meeting, citing weak human data and safety uncertainty.
FDA reviewers urge ‘no’ on BPC-157, TB-500, MOTS-c ahead of July 2026 compounding vote
FDA reviewers’ June 29 briefings recommend against listing seven popular peptides for 503A compounding, citing limited human data and immunogenicity risk.
Medicare Starts Paying for Obesity Drugs Today — Bridge Program Opens $50 Access for Millions
Medicare's new $50 Bridge program covering Wegovy, Zepbound, Foundayo, and oral Wegovy for obesity launched July 1 — the first Medicare weight-loss benefit.
FDA staff urges caution on compounded peptides ahead of July advisory meeting
Ahead of the July 23–24 Pharmacy Compounding Advisory Committee meeting, FDA staff briefings recommend against listing seven popular peptides for compounding.