Cagrisema

Mechanism

Cagrisema combines two complementary mechanisms:

1. Cagrilintide (amylin analogue) — mimics human amylin (islet amyloid polypeptide), which is co-secreted with insulin. Amylin acts on the area postrema of the hindbrain to promote satiety, slows gastric emptying via vagal pathways, and suppresses postprandial glucagon secretion. Cagrilintide is engineered with a C18 fatty acid side chain to extend its half-life, enabling once-weekly dosing.

2. Semaglutide (GLP-1 receptor agonist) — activates GLP-1 receptors in the pancreas (enhancing glucose-dependent insulin secretion), GI tract (slowing gastric emptying), and CNS (reducing appetite and food intake). Semaglutide is similarly modified with a fatty acid chain for extended half-life.

The combination targets distinct receptor systems (amylin and GLP-1) that converge on satiety and energy intake regulation, providing additive anorexigenic effects without overlapping receptor pharmacology.

Evidence base

Phase 2 Evidence

The Phase 2 dose-finding trial of cagrilintide in combination with semaglutide demonstrated that the combination produced meaningfully greater weight loss than semaglutide monotherapy or cagrilintide alone. A notable proportion of participants achieved ≥20% body weight reduction.

Published in The Lancet (2024), the cagrilintide monotherapy Phase 2 trial established the safety and efficacy profile of cagrilintide, supporting its advancement in combination with semaglutide.

Ongoing Phase 3 (REDEFINE Programme)

The REDEFINE Phase 3 programme (NCT05669599 and related trials) is evaluating Cagrisema versus semaglutide monotherapy and placebo across thousands of participants with obesity. Primary endpoints include percentage change in body weight and proportion achieving ≥25% weight loss. Results are anticipated to support regulatory submissions.

Limitations

• All available data originate from Novo Nordisk-sponsored trials; independent confirmation is pending.
• Phase 3 results are not yet published; the full safety and efficacy profile remains to be characterised.
• Long-term cardiovascular and renal outcome data are not yet available.

Protocols

Cagrisema is an investigational product with no approved dosing protocol outside clinical trials. In the Phase 2 and Phase 3 REDEFINE trials:

• Route: Subcutaneous injection (once weekly)
• Dose: Cagrilintide 2.4 mg + semaglutide 2.4 mg (fixed-dose combination)
• Titration: Gradual dose escalation over ~16 weeks to mitigate GI adverse effects
• Duration: Ongoing (trial-dependent)

No research-use protocols are established. The compound is not available from research peptide suppliers as a combination product.

UK legal status

UK Status: Prescription-only medicine (investigational, not licensed)

Cagrisema is not licensed by the MHRA and is not available on the NHS or through private prescription in the UK. As an investigational combination of cagrilintide and semaglutide:

• Semaglutide is a prescription-only medicine (POM) in the UK, licensed as Ozempic (type 2 diabetes) and Wegovy (weight management).
• Cagrilintide is not individually licensed in the UK or any other market.
• Cagrisema as a combination product has no regulatory approval anywhere in the world as of 2025.

For research purposes, the individual peptide components (cagrilintide, semaglutide) fall under the same UK regulatory framework as other research peptides — legal for bona fide research use but not licensed medicines. The combination product is not available from research peptide suppliers.

Vendor notes

Cagrisema is not commercially available as a combination product. The individual components — cagrilintide and semaglutide — may be available from UK research peptide vendors as separate products, but no vendor sells a pre-combined Cagrisema product. See the cagrilintide and semaglutide compound profiles for vetted UK vendor links.