Cagrilintide

Cagrilintide is a long-acting amylin analogue (peptide drug) from Novo Nordisk, given as a once-weekly subcutaneous injection. It binds to amylin receptors in the brainstem (area postrema, dorsal vagal complex), amplifies satiety signalling and reduces food intake. In a phase-3 REDEFINE 1 subanalysis (EASD 2025), cagrilintide 2.4 mg as monotherapy produced a mean weight reduction of 11.8 % over 68 weeks - with notably fewer gastrointestinal side effects than pure GLP-1 therapy. In the fixed combination with semaglutide 2.4 mg ("CagriSema"), mean weight loss reached about 20 % (NEJM 2025).

What is cagrilintide and how does it work?

Cagrilintide is a modified analogue of the incretin-related hormone amylin, which is co-secreted with insulin from pancreatic beta cells. Amylin acts primarily in the dorsal vagal complex (area postrema, nucleus of the solitary tract) and reduces appetite and food intake. Targeted acylation and amino-acid substitutions extend the plasma half-life to roughly one week, enabling once-weekly subcutaneous dosing.

• Target: amylin receptors (AMY-R with RAMP modulation) in the brainstem
• Effects: stronger satiety, less "food noise", slower gastric emptying
• Difference from GLP-1: not a GLP-1 receptor agonist - pharmacologically distinct, with its own side-effect profile

How strong is the clinical evidence?

The data set rests on several phase-1/2 trials and the phase-3 REDEFINE programme:

• Phase 2 (Lau et al., Lancet 2021, PMID 34798060): once-weekly, dose-dependent up to 4.5 mg s.c.
• Phase 1b combination (Enebo et al., Lancet 2021, PMID 33894838): cagrilintide + semaglutide 2.4 mg s.c., well tolerated
• REDEFINE 1 (Garvey et al., NEJM 2025, PMID 40544433): CagriSema vs. cagrilintide alone vs. semaglutide alone vs. placebo, n = 3,417, 68 weeks, ~20.4 % weight loss with the combination
• REDEFINE 2 (Davies et al., NEJM 2025, PMID 40544432): CagriSema in obesity with type 2 diabetes, n = 1,206
• EASD 2025 subanalysis of REDEFINE 1: cagrilintide 2.4 mg monotherapy - 11.8 % weight loss over 68 weeks, fewer GI side effects than GLP-1

This places the evidence at level 3: phase-3 data exist, but no monotherapy approval yet.

How does cagrilintide differ from GLP-1 drugs like semaglutide?

Where semaglutide acts via GLP-1 receptors, cagrilintide acts via amylin receptors. Both pathways dampen appetite and slow gastric emptying, but they are neuroanatomically and pharmacologically distinct. In REDEFINE 1 the combination (CagriSema) clearly outperformed either drug alone - the same dual-mechanism logic that drives tirzepatide (GLP-1/GIP) and retatrutide (GLP-1/GIP/glucagon).

What side effects are known?

• Mostly mild to moderate GI complaints (nausea, vomiting, diarrhoea) - fewer than with GLP-1 in the monotherapy subanalysis
• Local injection-site reactions
• Higher hypoglycaemia risk when combined with insulin or insulin secretagogues
• Long-term data on pancreatitis, thyroid C-cells and bone health are still pending

Regulatory status (as of September 2025)

Cagrilintide is not yet approved as a standalone product. Novo Nordisk's primary regulatory path is the fixed combination CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg, once-weekly s.c.). An FDA filing for CagriSema is expected on the basis of the REDEFINE data; a dedicated phase-3 monotherapy programme (RENEW) is set to start in Q4 2025.

For more background on the next peptide generation, see the phase-3 update on retatrutide and the post on the cardioprotective effect of semaglutide.

Note: This article is informational only and is not medical advice. It does not contain dosing instructions.