Cagrilintide

Overview

Cagrilintide is a long-acting acylated amylin analog developed by Novo Nordisk. It is investigational and not FDA-approved; Novo Nordisk's lead development path is the CagriSema co-formulation with semaglutide for weight management. Monotherapy cagrilintide was evaluated in Phase 2 but was deprioritized in favor of the combination.

Mechanism of Action

Cagrilintide is an amylin receptor agonist acting at AMY1/AMY3 complexes (calcitonin receptor + RAMP1/RAMP3) in the area postrema and nucleus tractus solitarius, with additional activity at the calcitonin receptor. It promotes postprandial satiety and slows gastric emptying. A C18 fatty diacid side chain enables reversible albumin binding and an extended half-life (~6 days) supporting once-weekly dosing. Paired with semaglutide, the amylin + GLP-1 mechanism produces complementary appetite suppression through distinct hypothalamic and brainstem pathways.

Research Summary

A Phase 2 dose-finding trial of cagrilintide monotherapy demonstrated dose-dependent weight loss of up to 10.8% over 26 weeks versus 3.0% for placebo (Lau et al., The Lancet, 2021). Novo Nordisk pivoted development to the CagriSema co-formulation with semaglutide 2.4 mg. The Phase 3 REDEFINE 1 trial (n=3,417, 68 weeks) in obesity reported ~22.7% mean body weight reduction on the treatment-policy estimand, with 91.9% achieving ≥5% weight loss versus 31.5% for placebo. Novo Nordisk submitted a CagriSema NDA to the FDA in December 2025; the application is under review in 2026. Cagrilintide is not FDA-approved as a standalone therapy, and CagriSema is not yet approved as of April 2026.

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)