Quick summary
CagriSema is a Novo Nordisk fixed-dose weekly co-formulation of cagrilintide (amylin analog) and semaglutide (GLP-1 agonist) at 2.4 mg each. It produced more than 20% mean weight loss in the REDEFINE 1 Phase 3 trial and is investigational, not yet FDA or EMA approved as of 2026.
Overview
CagriSema is a fixed-dose co-formulation combining cagrilintide (a long-acting amylin analogue) and semaglutide (a GLP-1 receptor agonist), both at 2.4 mg, administered as a single weekly subcutaneous injection. Developed by Novo Nordisk, it is the most effective weight-loss peptide combination in Phase 3 trials as of 2026, achieving mean body weight reductions exceeding 20% in non-diabetic adults over 68 weeks.
Mechanism of action
CagriSema harnesses two complementary appetite-regulating pathways. Semaglutide activates GLP-1 receptors in the hypothalamus, hindbrain, and vagus nerve, suppressing appetite, slowing gastric emptying, and improving insulin secretion. Cagrilintide mimics amylin, a pancreatic hormone co-secreted with insulin that acts on area postrema and nucleus tractus solitarius receptors to promote satiety, reduce food intake, and modulate glucagon secretion. The dual mechanism produces additive to synergistic appetite suppression through both hedonic and homeostatic neural pathways, which appears to underpin the superior weight loss versus either agent alone.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| weight management (investigational Phase 3 dose) | subcutaneous | 2400–2400 mcg | once weekly | Phase 3 protocol: escalate from lower doses over 16–20 weeks to target dose of 2.4 mg each component. Titration reduces GI adverse events. Investigational use only. |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
The REDEFINE 1 Phase 3 trial (68 weeks, non-diabetic adults with obesity) found a mean 20.4% body weight reduction with CagriSema versus 3.0% placebo. Approximately 60% of participants lost at least 20% of body weight, and 23% lost 30% or more. REDEFINE 2 (type 2 diabetes) showed 13.7% mean weight reduction. Both trials reported higher rates of gastrointestinal adverse events (79.6%) versus placebo (39.9%), primarily nausea, vomiting, and constipation, which were mostly transient and mild-to-moderate. Regulatory submission was anticipated in 2025–2026.[1][2][3]
Evidence grading
Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.
Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with CagriSema for synergistic effects.
Legal status
Not yet FDA or EMA approved as of 2026. Novo Nordisk is pursuing regulatory approval following Phase 3 REDEFINE data. Semaglutide and cagrilintide are individually in various approval stages. The co-formulation remains investigational.
Sourcing & access
Research compound
CagriSema is classified as a research compound. Regulatory status varies by jurisdiction. Always verify current legal status and source from vendors providing third-party certificates of analysis (COA).
Frequently asked questions
CagriSema is a fixed-dose co-formulation combining cagrilintide (a long-acting amylin analogue) and semaglutide (a GLP-1 receptor agonist), both at 2.4 mg, delivered as a single weekly subcutaneous injection by Novo Nordisk.
CagriSema engages two complementary appetite pathways. Semaglutide activates GLP-1 receptors in the hypothalamus, hindbrain, and vagus nerve to suppress appetite and slow gastric emptying, while cagrilintide mimics amylin and acts on the area postrema and nucleus tractus solitarius to promote satiety.
No. As of 2026 CagriSema is not yet FDA or EMA approved. Novo Nordisk is pursuing regulatory approval following the Phase 3 REDEFINE trial data, and the co-formulation remains investigational.
The REDEFINE 1 Phase 3 trial over 68 weeks in non-diabetic adults with obesity found a mean 20.4% body weight reduction with CagriSema versus 3.0% placebo. Approximately 60% of participants lost at least 20% of body weight and 23% lost 30% or more. REDEFINE 2 in type 2 diabetes showed 13.7% mean weight reduction.
The Phase 3 protocol is a single weekly subcutaneous injection delivering 2.4 mg each of cagrilintide and semaglutide, titrated up from lower doses over 16 to 20 weeks to reduce gastrointestinal adverse events.
The REDEFINE trials reported gastrointestinal adverse events in 79.6% of CagriSema patients versus 39.9% on placebo, primarily nausea, vomiting, and constipation. Most events were transient and mild to moderate. Other reported effects include diarrhea, abdominal pain, injection site reactions, decreased appetite, and fatigue.
Both target weight loss through dual mechanisms, but they use different receptor pairs. Tirzepatide is a single molecule that activates GLP-1 and GIP, while CagriSema is a co-formulation of semaglutide (GLP-1) and cagrilintide (amylin). CagriSema's REDEFINE 1 weight loss of 20.4% is comparable to tirzepatide's 22.5% in SURMOUNT-1.