Cagrilintide

In simple words

Cagrilintide is a copy of the hormone amylin, which helps you feel full. Paired with semaglutide in a single injection, it is studied for weight loss; in a large study, the combination produced about 20% weight loss.

What this molecule is

An amylin analog (32 aa), prolinated at position 29. CagriSema = cagrilintide + semaglutide in a single injection.

Why it is studied

REDEFINE 1 (NEJM 2025, n=3417): CagriSema → −20.4% over 68 weeks vs −14.9% (semaglutide) and −11.5% (cagrilintide). REDEFINE 2 (n=1206, T2D): −13.7%, HbA1c <6.5% in 73.5%.

How it works

Amylin component: CGRP receptor → ↓gastric emptying rate (stronger than GLP-1) + ↑satiation via the area postrema + ↑leptin sensitivity. GLP-1 component: standard. The synergy of the two mechanisms gives more than the sum of its parts.

Doses used in studies

CagriSema was used only in studies under medical supervision. In the REDEFINE 1 trial (phase III), cagrilintide was titrated every 4 weeks: 0.25 → 0.5 → 1.0 → 1.7 → 2.4 mg/week (maintenance dose 2.4 mg); doses up to 4.5 mg were studied in an earlier phase II. Administration once weekly SC.

Combined with in studies

• Tirzepatide — an alternative at a plateau on semaglutide

Level of evidence

Level A Human clinical trials. There are randomized controlled trials (RCTs), or the compound has been approved by a regulatory agency. The most reliable level. Phase III in NEJM 2025. FDA application submitted.

Important to know

Honest caveat: Not approved (2025). Approval is expected in 2026. Nausea at the start. In studies it was not combined with other GLP-1 agonists.

Studies in PubMed

1. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. (N Engl J Med, 2025)
2. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. (N Engl J Med, 2025)
3. Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. (Lancet, 2023)
4. Efficacy and Safety of Cagrilintide Alone and in Combination with Semaglutide (Cagrisema) as Anti-Obesity Medications: A Systematic Review and Meta-Analysis. (Indian J Endocrinol Metab, 2024)
5. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. (Lancet, 2021)
6. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial. (Lancet, 2021)