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Peptide Desk ReferencePDR
Metabolic/GLP-1InvestigationalEvidence: B

CagriSema

Also known as: Cagrilintide + Semaglutide, NNC9204-1706 + NNC9204-0530

GLP-1 Receptor AgonistAmylin AnalogueObesityType 2 Diabetes
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Investigational Compound. This compound is currently in clinical development and has not received regulatory approval. No established commercial regimen exists. Consult a qualified clinician for the latest information on clinical trial availability.

Overview

Clinical Summary

CagriSema is a fixed-dose combination of cagrilintide (amylin analogue) and semaglutide (GLP-1RA) administered as a single once-weekly subcutaneous injection. The dual-pathway approach targets complementary satiety and metabolic mechanisms. Phase 3 REDEFINE trials are evaluating CagriSema for obesity and type 2 diabetes.

Plain Language Summary

CagriSema combines two medications in a single weekly injection: semaglutide (which works on the GLP-1 pathway) and cagrilintide (which works on the amylin pathway). By targeting two different hunger-related hormone systems at once, it may produce greater weight loss than either medication alone. It is currently in late-stage clinical trials.

Mechanism of Action

CagriSema combines two complementary mechanisms: semaglutide activates GLP-1 receptors to enhance glucose-dependent insulin secretion, reduce appetite, and slow gastric emptying; cagrilintide activates amylin and calcitonin receptors to further suppress appetite via brainstem satiety centers and inhibit postprandial glucagon. The combination leverages distinct but synergistic neural and hormonal pathways for appetite suppression, potentially overcoming the weight loss plateau seen with GLP-1RA monotherapy.

Evidence Summary

Evidence Grade:Evidence: B

Phase 2 data demonstrated approximately 15.6% mean body weight loss at 32 weeks with CagriSema vs. 5.1% for cagrilintide alone and 8.0% for semaglutide alone. Phase 3 REDEFINE trials include REDEFINE 1 (obesity), REDEFINE 2 (T2D + obesity), and REDEFINE 3 (comparison vs. tirzepatide). Topline results from REDEFINE 1 reported approximately 22.7% weight loss at 68 weeks.

Safety Profile

The safety profile reflects the combined GI effects of both components. Nausea, vomiting, and diarrhea were more frequent during dose titration but generally transient. The incidence of GI adverse events was higher than with either component alone but led to low discontinuation rates in Phase 2. Class-specific warnings for GLP-1RAs (thyroid C-cell risk, pancreatitis) apply.

Contraindications

  • Personal or family history of medullary thyroid carcinoma
  • Multiple endocrine neoplasia type 2
  • Known hypersensitivity to semaglutide or amylin analogues
  • Pregnancy

Adverse Events

  • Nausea (most common)
  • Diarrhea
  • Vomiting
  • Constipation
  • Injection site reactions
  • Decreased appetite

Interactions

  • Oral medication absorption may be delayed
  • Caution with insulin or sulfonylureas
  • No formal interaction studies for the combination

Regulatory Notes

CagriSema is in Phase 3 development under Novo Nordisk. No regulatory approval has been granted. Regulatory filing is anticipated following completion of the REDEFINE program. The combination is not available outside of clinical trials or research settings.

Monitoring Considerations

Standard metabolic monitoring. Monitor GI tolerability closely during dose escalation. Thyroid monitoring per GLP-1RA class guidance. Weight and body composition tracking.

These are general considerations for clinical awareness and do not constitute prescriptive monitoring recommendations for any individual patient.

Stability and Handling Notes

Fixed-dose combination investigational product. Not commercially available.

References

  1. 1
    RCT

    Once-Weekly Cagrilintide for Weight Management in People with Overweight and Obesity

    Enebo LB, Berthelsen KK, Kankam M, et al. (2021). New England Journal of Medicine

    Key findings: Phase 2 trial. Dose-dependent weight loss up to 10.8% at 26 weeks with cagrilintide monotherapy.

    Limitations: 26-week duration. Small sample size per dose group.

    View source
  2. 2
    RCT

    CagriSema Phase 2 Trial: Cagrilintide Plus Semaglutide for Weight Loss

    Frias JP, Deenadayalan S, Erichsen L, et al. (2023). Nature Medicine

    Key findings: CagriSema achieved approximately 15.6% weight loss at 32 weeks vs 5.1% cagrilintide and 8.0% semaglutide alone.

    Limitations: Phase 2 study. Open-label dose escalation phase followed by randomized period.

    View source
  3. 3
    RCT

    REDEFINE 1: CagriSema Phase 3 Trial Top-Line Results

    Novo Nordisk Press Release (2024). Novo Nordisk Corporate Communications

    Key findings: CagriSema achieved approximately 22.7% weight loss at 68 weeks in Phase 3. Full peer-reviewed data pending.

    Limitations: Top-line results only; full publication not yet available.

Last reviewed: 2024-12-01 | Version: 1 | Status: Published