Cagrilintide

Research · Cagrilintide

Overview

Cagrilintide is a long-acting synthetic analog of amylin, a hormone co-secreted with insulin by pancreatic beta cells. First described by Novo Nordisk researchers, the sequence incorporates amino acid substitutions that reduce the fibrillation tendency of native amylin and an N-terminal C-20 fatty diacid moiety that enables albumin binding. These modifications extend the systemic half-life to roughly one week. It is investigated both as a single agent and in combination with GLP-1 receptor agonists in metabolic research.

Mechanism of action

Cagrilintide is a nonselective agonist of the amylin receptors (AMY1, AMY2 and AMY3), which are heterodimers of the calcitonin receptor with receptor activity-modifying proteins, and it also activates the calcitonin receptor itself. Amylin receptor signaling in the area postrema and other hindbrain and hypothalamic regions is associated with enhanced satiation and reduced food intake. Peripheral effects include slowed gastric emptying and suppression of postprandial glucagon secretion. These pathways are distinct from, and proposed to be complementary to, GLP-1 receptor signaling.

Key research findings

1. 01

   Medicinal chemistry studies describe the design of the acylated analog, characterizing receptor potency, physical stability in solution, and pharmacokinetics supporting extended exposure.

2. 02

   Preclinical rodent studies characterized dose-dependent reductions in food intake and body weight consistent with amylin receptor agonism, with effects sustained over repeated exposure.

3. 03

   A dose-finding phase 2 clinical trial characterized body weight endpoints against placebo and an active GLP-1 receptor agonist comparator, with gastrointestinal events as the most commonly reported adverse events.

4. 04

   Clinical pharmacology studies have characterized pharmacokinetics in participants with renal or hepatic impairment, reporting no clinically relevant change in exposure, and in co-administration with semaglutide.

Published references

• Development of Cagrilintide, a Long-Acting Amylin Analogue

  Kruse T et al. — J Med Chem, 2021 · PMID: 34288673

• 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

  Lau DCW et al. — Lancet, 2021 · PMID: 34798060

The information above is derived from published preclinical and clinical research. It is provided for educational purposes only and does not constitute medical advice, diagnosis, or treatment recommendations.