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Long-acting amylin analog · Cagrilintide

Cagrilintide research and evidence overview

The state of evidence for cagrilintide — a phase 2 dose-finding trial in 906 people, a head-to-head result against liraglutide, and a development path that has largely folded it into a combination product.

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Quick facts

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

Cagrilintide is an investigational drug. It has no FDA-approved indication as a standalone product. The trial results below come from manufacturer-sponsored studies.

The short answer

Cagrilintide is clinical-stage, not experimental-peptide territory: it has a published, multicentre, randomised, double-blind phase 2 trial with more than 900 participants, real numbers, and an active comparator. On its own it produced roughly 10.8% weight loss at the top dose over 26 weeks — a genuine effect, and one that beat liraglutide 3.0 mg. What it lacks is a standalone phase 3 programme and an approval, because the developer's attention moved to pairing it with semaglutide.

The phase 2 dose-finding trial

The defining study is a phase 2 dose-finding trial across 57 sites in 10 countries (Lau et al., The Lancet 2021). Participants with overweight or obesity were randomised to once-weekly cagrilintide across a dose range of 0.3 mg to 4.5 mg (706 people across the dose arms), liraglutide 3.0 mg (99), or placebo (101), for 26 weeks of treatment plus 6 weeks of follow-up.

Mean percentage weight reduction from baseline was greater at every cagrilintide dose than on placebo: 6.0% to 10.8% (6.4–11.5 kg) across the dose range, versus 3.0% (3.3 kg) on placebo, p<0.001. The dose-response was orderly, which is what a dose-finding trial is for — the effect scaled with dose rather than appearing only at one arbitrary level.

Amylin, the hormone cagrilintide mimics, is co-secreted with insulin and slows gastric emptying while promoting satiety through the area postrema — a different pathway from GLP-1, which is why the combination idea followed.

The head-to-head against liraglutide

The trial's most informative comparison is often skipped: cagrilintide 4.5 mg was tested against liraglutide 3.0 mg, an approved GLP-1 weight-management drug, in the same study. Weight reduction was 10.8% (11.5 kg) with cagrilintide versus 9.0% (9.6 kg) with liraglutide, p=0.03. A statistically significant but modest margin over an approved comparator, in a 26-week phase 2 trial, is a real result — and a smaller gap than the way this drug is sometimes described would suggest.

Tolerability followed the familiar pattern for this drug class. Gastrointestinal events — nausea, constipation, diarrhoea — were the most frequent adverse events, occurring in 41% to 63% of cagrilintide recipients versus 32% on placebo, alongside administration-site reactions.

Cagrilintide as a combination component

Most subsequent cagrilintide data come from trials where it is one half of CagriSema. In a 32-week phase 2 trial in type 2 diabetes, the cagrilintide-only arm (n=30, escalated to 2.4 mg) produced a mean weight change of −8.1% and an HbA1c reduction of 0.9 percentage points, against −15.6% and −2.2 points for the combination (Frias et al., The Lancet 2023, PMID 37364590). The 68-week phase 3a REDEFINE 1 trial also included a cagrilintide-alone arm of 302 participants among its 3,417 randomised (Garvey et al., NEJM 2025, PMID 40544433).

Reading those numbers fairly: cagrilintide alone works, and works less well than the combination. Its role in the development programme is now largely as a component rather than a product.

Regulatory status and open questions

Cagrilintide is not FDA-approved as a standalone medicine, and it is not available by prescription on its own. The published evidence covers 26 to 32 weeks of treatment in most trials; durability beyond that, weight regain after stopping, cardiovascular outcomes, and long-term safety have not been reported for cagrilintide monotherapy. Every trial cited here was funded by the manufacturer, which is standard for drug development and still worth stating.

Material sold as "cagrilintide" outside a clinical trial or an approved supply chain is not the manufactured product used in these studies, and its identity, purity, and concentration are not independently verified.

References

  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

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

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