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phase 3Weight Loss & Diabetes

CagriSema

Also known as: Cagrilintide/Semaglutide, NNC9204-1706/Semaglutide

CagriSema is a fixed-ratio co-formulation of cagrilintide (a long-acting amylin analog) and semaglutide 2.4 mg (GLP-1 RA) under development by Novo Nordisk for obesity and type 2 diabetes. Phase 3 REDEFINE trials demonstrated up to 22–25% body weight loss at 68 weeks, potentially surpassing semaglutide 2.4 mg alone. CagriSema targets both the GLP-1 and amylin pathways simultaneously for additive weight loss effects.

4 cited references·5 researched benefits

Quick Answer

CagriSema is a once-weekly injectable combination of cagrilintide (amylin analog) and semaglutide 2.4 mg (GLP-1 agonist) in development by Novo Nordisk for obesity treatment. By targeting both GLP-1 and amylin receptors simultaneously, phase 3 REDEFINE trials show 22–25% body weight loss at 68 weeks — exceeding semaglutide alone. It represents a next-generation approach to pharmacological weight management through dual-pathway appetite suppression.

Key Facts

Mechanism
CagriSema combines two complementary mechanisms. Cagrilintide is a long-acting analog of amylin (a 37-amino-acid peptide co-secreted with insulin from pancreatic beta cells) that activates amylin receptors (calcitonin receptor + RAMP complexes) in the area postrema and nucleus tractus solitarius, reducing appetite and food intake. Semaglutide activates GLP-1 receptors in the hypothalamus, gut, and pancreas, suppressing appetite, slowing gastric emptying, and enhancing glucose-dependent insulin secretion. The dual activation of these distinct but complementary satiety pathways produces additive weight loss beyond either agent alone.
Research Status
phase 3
Half-Life
~7 days (both components)
Primary Use
Weight Loss & Diabetes
Table of Contents

Benefits

  • Superior weight loss — 22–25% body weight reduction in phase 3 REDEFINE trials at 68 weeks, exceeding semaglutide 2.4 mg monotherapystrong
  • Dual pathway mechanism — simultaneous amylin and GLP-1 receptor activation provides additive appetite suppressionstrong
  • Glycemic improvement — substantial HbA1c reductions in patients with type 2 diabetes and obesitystrong
  • Single weekly injection — both agents co-formulated in one pen for patient conveniencestrong
  • Potential cardiometabolic benefits — weight loss magnitude associated with improvements in blood pressure, lipids, and inflammatory markersmoderate

Dosage Protocols

RouteDosage RangeFrequencyNotes
Subcutaneous injectionCagrilintide 2.4 mg + Semaglutide 2.4 mg (target dose)Once weeklyDose escalation over 16–20 weeks with stepwise increases of both components. Phase 3 trials use escalation from low starting doses to minimize gastrointestinal side effects.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Nausea — most common adverse event (40–50%), typically during dose escalation and diminishing over timecommon
  • Vomiting — reported in 15–20% of patients during titration phasecommon
  • Diarrhea and constipation — gastrointestinal events in 10–15% of patientscommon
  • Injection-site reactions — mild erythema or bruising at injection sitecommon
  • Cholelithiasis — gallbladder events reported at rates consistent with rapid weight loss (~2–3%)rare

Frequently Asked Questions

How does CagriSema compare to tirzepatide for weight loss?
Both CagriSema and tirzepatide represent next-generation obesity treatments with >20% weight loss potential. CagriSema combines amylin + GLP-1 pathways, while tirzepatide targets GIP + GLP-1 receptors. No head-to-head trials exist yet. Phase 3 data suggests CagriSema achieves 22–25% weight loss versus tirzepatide's 20–26% (SURMOUNT-1). Both significantly exceed semaglutide 2.4 mg monotherapy (15–17%). Direct comparisons will determine which approach is superior.
What is cagrilintide and why is it combined with semaglutide?
Cagrilintide is a long-acting analog of amylin, a peptide hormone co-secreted with insulin that signals satiety through brain receptors in the area postrema. While pramlintide (the only approved amylin analog) requires three-times-daily dosing, cagrilintide was engineered for once-weekly administration. Combining it with semaglutide adds GLP-1 pathway activation, targeting two distinct appetite control centers for additive weight loss that exceeds either agent alone by 5–8 percentage points.
When will CagriSema be available?
Novo Nordisk submitted CagriSema for FDA regulatory review based on positive phase 3 REDEFINE trial results. If approved, commercial availability is anticipated in late 2026 or early 2027. The regulatory timeline depends on review speed and potential advisory committee meetings. Manufacturing scale-up is critical given ongoing GLP-1 RA supply constraints.
What are the REDEFINE trials?
REDEFINE is the phase 3 clinical trial program for CagriSema, comprising multiple studies: REDEFINE 1 (obesity without diabetes), REDEFINE 2 (obesity with type 2 diabetes), and additional studies for specific populations. REDEFINE 1 showed approximately 22–25% weight loss at 68 weeks. The program enrolled thousands of participants globally and provides the registration data for FDA and EMA submissions.
Will CagriSema be covered by insurance?
Insurance coverage will depend on regulatory approval indications and payer negotiations. If approved for obesity (not just diabetes), coverage could mirror the current landscape for Wegovy — limited commercial coverage with prior authorization requirements and varying out-of-pocket costs. Medicare Part D coverage for anti-obesity medications may expand depending on legislative changes. Novo Nordisk has not disclosed planned pricing.

References

  1. 1
    Cagrilintide plus semaglutide 2.4 mg for weight management: a phase 2, randomised, double-blind, placebo-controlled trial(2023)PubMed ↗
  2. 2
    Once-weekly cagrilintide for weight management in people with overweight and obesity (REDEFINE 1)(2024)PubMed ↗
  3. 3
    Amylin physiology and its pharmacotherapy for obesity(2022)PubMed ↗
  4. 4
    Dual amylin and GLP-1 receptor agonism: rationale and emerging therapeutic approaches for metabolic disease(2022)PubMed ↗

Latest Research

Last updated: 2026-02-19