Cagrilintide

Overview

Cagrilintide is a long-acting acylated amylin analog developed by Novo Nordisk. It is under investigation as a weight management compound, both as a monotherapy and in combination with semaglutide (CagriSema), targeting amylin receptor-mediated satiety pathways.

Mechanism of Action

Cagrilintide activates amylin receptors (AMY1 and AMY3) in the area postrema and nucleus of the solitary tract, promoting satiety signaling and slowing gastric emptying. A C18 fatty diacid side chain enables albumin binding and extended half-life (~7 days). When combined with semaglutide, the dual amylin/GLP-1 mechanism produces complementary appetite suppression through distinct hypothalamic and brainstem pathways.

Research Summary

The Phase II REDEFINE trial demonstrated dose-dependent weight loss of up to 10.8% over 26 weeks versus 3.0% for placebo (Lau et al., The Lancet, 2021). The Phase III REDEFINE 1 trial of CagriSema showed approximately 22-25% mean body weight reduction at 68 weeks, exceeding semaglutide monotherapy. Novo Nordisk submitted CagriSema for FDA review in late 2024.

Dosing Information

Reported Side Effects

• Nausea (dose-dependent, most common adverse event)
• Injection site reactions (erythema, pain, pruritus)
• Diarrhea
• Vomiting
• Constipation

Research References

• 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 (2021)
• Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management (2021)