Summary

CagriSema is an investigational once-weekly combination of cagrilintide (a long-acting amylin analogue) and semaglutide (a GLP-1 receptor agonist), both developed by Novo Nordisk. The REDEFINE-2 Phase 3 trial (published in NEJM, 2025; PubMed: 40544432) demonstrated that CagriSema achieved −13.0% mean weight loss at 68 weeks in adults with type 2 diabetes and obesity, superior to both placebo (−5.0%) and semaglutide alone. It is the first Phase 3 evidence that combining an amylin analogue with a GLP-1 agonist produces superior weight loss compared with GLP-1 monotherapy. CagriSema is not yet licensed in the UK or any market.

Mechanism

CagriSema combines cagrilintide (a long-acting amylin analogue with a C18 fatty acid chain for extended half-life) and semaglutide (a GLP-1 receptor agonist). Amylin receptor activation promotes satiety, delays gastric emptying, and suppresses glucagon, while GLP-1 receptor activation enhances insulin secretion, suppresses glucagon, and reduces appetite. The combination targets complementary pathways for additive weight-loss effects.

Protocols

In the REDEFINE-2 trial, CagriSema was administered as a once-weekly subcutaneous injection at a target dose of cagrilintide 2.4 mg / semaglutide 2.4 mg, with dose escalation to mitigate gastrointestinal side effects. This is an investigational therapy — for research/educational context only.

CagriSema is not yet licensed in the UK or any market. It is an investigational combination therapy under development by Novo Nordisk with no current MHRA marketing authorisation. Both components are regulated substances — semaglutide is a UK POM. Any unauthorised supply falls under UK medicines legislation. The REDEFINE-2 data (NEJM, 2025) may support future MHRA/EMA regulatory submissions.

Vendor notes

CagriSema is not commercially available as it is not yet licensed. Individual components (cagrilintide and semaglutide) are available from select UK research chemical suppliers for in vitro and preclinical research purposes only — not for human use. See vetted vendor listings for suppliers with appropriate research-grade product lines.

References

  1. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2). N Engl J Med, 2025;393:648-659. PubMed: 40544432.
  2. Eneberg C, et al. "Cagrilintide and Semaglutide Combination Therapy: Phase 2 Results." Diabetes, 2021.
  3. Novo Nordisk. "REDEFINE clinical programme." ClinicalTrials.gov: NCT05394519 (REDEFINE-2).
  4. MHRA. "GLP-1 receptor agonists: review of benefits and risks." GOV.UK Drug Safety Updates, 2024–2025.