Cagrilintide — a long-acting amylin analogue: mechanism and scientific evidence

Cagrilintide is a synthetic analogue of amylin, a hormone the pancreas releases together with insulin. Novo Nordisk designed it to act for a week and studies it mainly in combination with semaglutide under the name CagriSema. In December 2025 the company filed an application with the US FDA for approval of that combination as a medicine for obesity. No decision had been issued at the time of publication.

This article explains what amylin is and why its analogues were unsuitable as medicines for so long. It shows what cagrilintide changed, what the phase 2 and phase 3 trials found, and what the legal and anti-doping status is. Semaglutide appears here only as the partner in CagriSema, because it has its own monograph. You will find no dose figures outside the context of clinical trials here; the reasoning is given in the FAQ section.

In our catalogue, the compounds discussed in this article are chemical reagents intended solely for laboratory research (Research Use Only). They are not medicinal products, dietary supplements or foods, and they are not intended for use in humans or animals. What this status means is explained in our material on the legal status of research reagents.

An essential distinction: every figure on body-weight reduction in this article comes from clinical trials of a drug candidate, run under medical supervision with semaglutide, which is a prescription medicine (Ozempic®, Wegovy®). Research material containing the same peptide is not a substitute for a medicinal product and does not replace medical consultation. The clinical trial findings do not apply to it.

Amylin: a hormone that was hard to turn into a medicine

Amylin is a 37-amino-acid peptide released by pancreatic β-cells together with insulin after a meal. Its receptors are unusual: they are formed by the calcitonin receptor combined with RAMP proteins, which gives several subtypes. The hormone acts primarily in the brainstem, in the area postrema, where the blood–brain barrier is permeable (Hay et al., 2015, PMID 26071095). The effect is threefold: slower gastric emptying, less glucagon release and an earlier end to the meal.

That last effect, satiation during a meal, is rapid and short-lived, because it mirrors the post-meal rise in hormone levels. Amylin also lowers the rewarding value of food, and in people its agonists reduced the number of binge-eating episodes (Lutz, 2025, PMID 40639451). For obesity treatment, this is a mechanism distinct from the incretin one, which is why combining it with GLP-1 agonists has been considered for years.

The problem lay in the chemistry. Human amylin forms amyloid fibrils very readily, the same fibrils that build up in the pancreas in type 2 diabetes. The first analogue, pramlintide, solved this by substituting three amino acids. It has a short half-life, though, and has to be given more than once per day (Kruse et al., 2021, PMID 34288673). FDA approved it in 2005 as the medicine Symlin® for type 1 and type 2 diabetes in people treated with insulin (Drugs@FDA, NDA 021332). It has never been registered as a medicine for obesity.

What cagrilintide is

Cagrilintide is a stable, lipidated amylin analogue. Novo Nordisk’s chemists changed the sequence so that the peptide does not aggregate and attached a fatty-acid chain that binds albumin and prolongs its time in the blood. As a result, in the clinical trials one dose lasted a week. The paper describing the molecule’s design appeared in 2021 and names obesity outright as the indication for which this analogue was chosen (Kruse et al., 2021).

The first large trial, a phase 2 study of 706 adults with obesity or overweight and no diabetes, ran for 26 weeks in ten countries, Poland among them. Under the estimand assuming adherence to treatment, body weight fell by 6.0% to 10.8% depending on the dose, against 3.0% in the placebo group. The highest dose produced a larger effect than liraglutide given once a day: 10.8% against 9.0%. The most frequent adverse events were gastrointestinal, and nausea was reported by 20% to 47% of participants against 18% on placebo (Lau et al., 2021, PMID 34798060).

Those findings placed cagrilintide in a new group of long-acting amylin analogues, which today also includes eloralintide, petrelintide and several compounds with code names. A 2026 review regards this group as the next major class of obesity medicines, alongside GLP-1 agonists (Alhazmi and le Roux, 2026, PMID 42452898). None of these compounds is yet a registered medicine.

CagriSema: the clinical trial programme

The idea is simple: combine two satiety mechanisms, the amylin one and the incretin one, in a single weekly administration. A phase 1b trial with 96 participants tested whether the two peptides can be given together. Cagrilintide exposure rose in proportion to the dose and did not change semaglutide exposure, and most adverse events were mild or moderate (Enebo et al., 2021, PMID 33894838).

A phase 2 trial in 92 people with type 2 diabetes lasted 32 weeks. Glycated haemoglobin fell by 2.2 percentage points on CagriSema, against 1.8 on semaglutide alone and 0.9 on cagrilintide alone. Body weight fell by 15.6%, 5.1% and 8.1% respectively (Frias et al., 2023, PMID 37364590). The HbA1c difference between CagriSema and semaglutide was not statistically significant; the body-weight difference was.

The main phase 3 trials are called REDEFINE. REDEFINE 1 enrolled 3,417 adults with obesity or overweight and no diabetes. After 68 weeks, body weight fell by 20.4% on CagriSema against 3.0% on placebo, under the treatment-policy estimand, which counts all participants regardless of adherence. Gastrointestinal adverse events were reported by 79.6% of people on CagriSema and 39.9% on placebo (Garvey et al., 2025, PMID 40544433).

REDEFINE 2 enrolled 1,206 adults with type 2 diabetes. Here the reduction was 13.7% against 3.4% on placebo, again under the treatment-policy estimand. An HbA1c level of 6.5% or lower was reached by 73.5% of people on CagriSema and 15.9% on placebo (Davies et al., 2025, PMID 40544432). Both trials were funded by the manufacturer, which is the norm for registration trials and does not invalidate the findings, but it needs to be noted.

The most difficult result came from REDEFINE 4, an open-label comparison with tirzepatide in 809 adults with obesity. After 84 weeks, CagriSema produced a 23.0% reduction against 25.5% on tirzepatide under the efficacy estimand, and 20.2% against 23.6% under the treatment-regimen estimand. The trial did not meet its primary objective, which was to show that CagriSema is non-inferior (Novo Nordisk, 23 February 2026). The company announced a phase 3 trial with a higher dose of the combination for the second half of 2026. The REDEFINE 11 readout is expected in the first half of 2027.

Safety and tolerability in the trials

The adverse-event profile of cagrilintide resembles that of GLP-1 agonists. Nausea, constipation and diarrhoea dominate, usually transient and mild or moderate in severity (Lau et al., 2021; Garvey et al., 2025). In the phase 1b trial most events were mild or moderate, and the proportion of participants with at least one event was similar across groups (Enebo et al., 2021). A thorough QT study in 105 healthy volunteers showed no clinically relevant prolongation of the QTc interval (Gabe et al., 2024, PMID 39279639).

A meta-analysis of three randomised trials (3,545 participants) compared CagriSema and cagrilintide alone with semaglutide. The combination produced 7.5 percentage points more body-weight reduction than semaglutide, while cagrilintide alone was comparable to semaglutide. The price was more frequent administration-site reactions and nausea, and with cagrilintide monotherapy more frequent serious adverse events than with semaglutide (Ahmed et al., 2026, PMID 41834765). The authors also noted slightly higher LDL cholesterol with the combination.

The answer about effects on the heart and blood vessels has to wait. The REDEFINE 3 trial enrolled 7,076 adults with established cardiovascular disease at 575 sites in 24 countries. Its safety objective is to show that CagriSema does not raise the risk of cardiovascular death, heart attack and stroke compared with placebo. Its efficacy objective is superiority on a broader composite endpoint (Cavender et al., 2026, PMID 42838477). In the REIMAGINE 3 trial in type 2 diabetes treated with basal insulin, CagriSema lowered HbA1c by 2.3 percentage points against 0.7 on placebo after 40 weeks (efficacy estimand). No severe hypoglycaemia was recorded (Rosenstock et al., 2026, PMID 42251856).

What these numbers mean, and what they do not

Each value given here describes a specific clinical programme. It had a defined population, a dose raised step by step under physicians’ supervision, a lifestyle intervention in every group and a stated estimand. That is why we mark next to each number whether it refers to participants who adhered to treatment or to everyone randomised. The same molecules outside a clinical trial have none of that framework.

From this follows a sentence we put first in the semaglutide article and repeat here. The REDEFINE findings belong to a drug candidate under FDA review, not to research material sold outside the pharmacy channel. A reagent with the cagrilintide sequence, even one of confirmed purity, has not passed the quality control required of a medicine and has no package leaflet. Nobody has studied it in humans. The comparison of the two incretin agonists, which REDEFINE 4 settled in tirzepatide’s favour, is discussed in our separate article on tirzepatide and semaglutide.

Regulatory status

European Union. Cagrilintide is not a registered medicine in the EU, and the EU medicines data published by EMA under Article 57 contain no entry for it (as of 9 October 2026). Novo Nordisk’s releases of December 2025 and February 2026 say nothing about an application in the EU. They do state that CagriSema is not approved in the US or the EU (Novo Nordisk, 18 December 2025).

United States. Drugs@FDA lists no product containing cagrilintide (checked 1 November 2026). The only route to registration today runs through CagriSema. On 18 December 2025, Novo Nordisk submitted a New Drug Application to FDA for the fixed-dose combination of cagrilintide and semaglutide. The indication sought is reducing excess body weight and maintaining that reduction in adults with obesity, or with overweight and at least one weight-related condition. The application rests on REDEFINE 1 and 2, and the company expected the review to take place in 2026 (Novo Nordisk, 18 December 2025). By 1 November 2026 FDA had not decided; in its February 2026 release the company anticipated a decision by late 2026. Cagrilintide is not on FDA’s 503A Bulks List for pharmacy compounding either.

Other countries. No governmental health authority anywhere has approved cagrilintide as a medicine, alone or in combination. The Cagrilintide 5 mg page describes the same state: a reagent with no medicinal registration.

Anti-doping note

Cagrilintide is not named on the WADA 2026 Prohibited List. What decides the matter is class S0, which covers every pharmacological substance with no approval for human use from any governmental regulatory authority, including medicines in clinical development. Cagrilintide is in exactly that position: it falls under class S0, prohibited at all times. From 1 January 2027 the 2027 List applies, which names “peptides” in class S0 explicitly (USADA, 2026). USADA, which applies the WADA List to athletes in the United States, published the summary of the 2027 changes on 6 October 2026.

Semaglutide has a different status. As a registered medicine it is not in S0 and is not prohibited, while WADA keeps it under the 2026 Monitoring Program, which is not a ban. If FDA approved CagriSema, cagrilintide would become a component of an approved medicine and the basis for class S0 would fall away. Until then, the status is unambiguous. How the classification works is described in our guide to the WADA Prohibited List; WADA and the national agencies have the final say.

Frequently asked questions

What is the cagri peptide?
A colloquial name for cagrilintide, Novo Nordisk’s long-acting amylin analogue. In clinical trials it was given once a week, alone or with semaglutide.

Is cagrilintide the same as CagriSema?
No. CagriSema is the combination of cagrilintide with semaglutide, under FDA review as a drug candidate. Cagrilintide alone was tested in phase 2 and as a comparator arm in the phase 3 trials.

Is cagrilintide a registered medicine?
No, not in any country. The application for approval concerns the combination with semaglutide and has been with FDA since December 2025, with no decision as of publication.

How much body weight was lost in the trials?
In REDEFINE 1, an average of 20.4% after 68 weeks against 3.0% on placebo, counting everyone randomised. In the comparison with tirzepatide in REDEFINE 4, CagriSema did worse. The figures concern a drug candidate in a clinical trial, not a reagent.

Cagrilintide dosing: why do we leave this subject out?
The doses in the REDEFINE programme belong to a drug candidate and were raised step by step under medical supervision. They do not carry over to research material, which must not be given to humans.

Is cagrilintide prohibited in sport?
Yes. As a substance with no approval as a medicine, it falls under class S0 of the WADA List, prohibited at all times. Semaglutide, its partner in CagriSema, is not prohibited and is only monitored.

Summary

Cagrilintide is a lipidated amylin analogue with a week-long action that solved the aggregation problem limiting pramlintide. In phase 2 it produced up to 10.8% body-weight reduction in 26 weeks. Combined with semaglutide as CagriSema, it produced 20.4% in 68 weeks in REDEFINE 1 and 13.7% in people with type 2 diabetes in REDEFINE 2. In the open-label comparison REDEFINE 4 it lost to tirzepatide. The application to register CagriSema has been with FDA since December 2025, and cagrilintide itself is not a medicine anywhere, which settles class S0 on the WADA List. Every finding belongs to clinical trials of a drug candidate, not to research material.

Product documentation

Reagent page with batch documentation: Cagrilintide 5 mg. Combinations with semaglutide: SEMA + CAGRI PEN (2 + 2), SEMA + CAGRI PEN (4 + 4) and Semaglutide + Cagrilintide. Compounds studied in the context of body-weight reduction are collected in the fat burners category. The mechanisms of this group are set out in our guide to effective fat burners. Triple agonism is covered in a separate article on retatrutide. Each batch’s identity and purity are documented in a certificate of analysis.

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