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Long-acting amylin analog · Cagrilintide

Cagrilintide potential benefits and areas of research

The trial-measured effects of cagrilintide, a long-acting amylin analog — up to 10.8% weight loss alone at 26 weeks, more when combined with semaglutide — and why an amylin mechanism matters in a GLP-1 world.

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Quick facts

Family
GLP-1 / incretin
About
Long-acting amylin analog studied for chronic weight management, usually alongside a GLP-1 receptor agonist.
Investigational agent

Cagrilintide is an investigational long-acting amylin analog developed by Novo Nordisk. It is not approved as a standalone therapy anywhere. The numbers below come from supervised clinical trials of pharmaceutical-grade product.

Overview

Cagrilintide's demonstrated benefit is weight loss: in its 26-week phase 2 dose-finding trial it produced 6.0–10.8% average weight reduction versus 3.0% with placebo, and at the top dose it modestly out-performed liraglutide 3.0 mg, an approved weight-loss drug. It is a long-acting analog of amylin — a hormone the pancreas co-secretes with insulin after meals — which makes it mechanistically distinct from the GLP-1 drugs that dominate this space. Its bigger role, though, is as the amylin half of CagriSema, where the combination roughly doubled what semaglutide achieved alone in phase 2 diabetes data.

The phase 2 numbers, alone

The key standalone evidence is a 706-person, 26-week, placebo- and active-controlled phase 2 dose-finding trial run at 57 sites in 10 countries, enrolling adults without diabetes who had a BMI of 30 or more (or 27 with hypertension or dyslipidemia) (Lancet 2021):

  • Once-weekly cagrilintide 0.3–4.5 mg produced 6.0–10.8% average weight loss, dose-dependently, versus 3.0% with placebo.
  • At 4.5 mg, weight loss was 10.8% vs 9.0% for liraglutide 3.0 mg — the first sign an amylin analog could compete with an approved GLP-1 drug.
  • Weight had not plateaued at 26 weeks, suggesting longer treatment would show more — a hypothesis the longer combination trials later supported.

What it adds to semaglutide

The commercial logic of cagrilintide is additive. In a phase 1b trial, co-administering cagrilintide with semaglutide 2.4 mg for 20 weeks produced up to 17.1% weight loss versus 9.8% for semaglutide plus placebo (Lancet 2021). In the 68-week phase 3 REDEFINE 1 trial of the fixed combination, weight loss reached 20.4% (NEJM 2025). Those combination results — covered in depth on the CagriSema page — are the reason cagrilintide exists as a development program.

Why an amylin mechanism is different

Amylin signals satiety mainly through receptors in the hindbrain and slows gastric emptying — an appetite pathway parallel to, not overlapping with, GLP-1. Two practical consequences follow. First, amylin signaling can add to GLP-1 effects rather than duplicating them, which is the entire premise of CagriSema. Second, some researchers hypothesize amylin agonism produces a different quality of appetite suppression; that idea is under active study with cagrilintide and newer amylin analogs, not settled. There is precedent for the class working in humans: pramlintide, a short-acting amylin analog, has long been approved as a mealtime adjunct in diabetes — cagrilintide's innovation is a lipidated, albumin-binding structure that stretches amylin signaling across a full week from one injection.

The caveats

  • Cagrilintide alone has completed phase 2, not phase 3 — its standalone efficacy rests on one 26-week trial, though the REDEFINE 1 monotherapy arm will add longer data as analyses publish.
  • Every number above comes from titrated, pharmaceutical-grade product given under supervision; "research-grade" vials sold online are not the studied article.
  • Weight regain after stopping — well documented for this drug class — means benefits are conditional on continued treatment.
  • Gastrointestinal side effects were common in trials — nausea alone affected up to 47% of participants; see the side-effects page for the full rates.

Keep reading

Key studies

Curated primary literature for Cagrilintide. Links open the publisher or PubMed record in a new tab.

  1. 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 trialPubMed

Search the literature

PubMed · ClinicalTrials.gov · Google Scholar