Cagrilintide
A lipidated amylin analogue dosed weekly: up to 10.8% weight loss on its own in phase 2, and the partner to semaglutide in CagriSema
Cagrilintide is a long-acting, lipidated analogue of amylin, a pancreatic hormone that promotes fullness, developed by Novo Nordisk to avoid amylin's tendency to form fibrils and the three daily injections of the older analogue pramlintide. On its own, once weekly, it reduced weight by up to 10.8% over 26 weeks in a phase 2 trial. Combined with semaglutide as CagriSema, weight fell 20.4% over 68 weeks in the phase 3 REDEFINE 1 trial. It is investigational.
What is it?
Amylin is a 37-amino-acid hormone that the pancreas releases alongside insulin after meals. It slows stomach emptying, blunts the after-meal rise in glucagon and signals fullness to the brain. As a drug it has two problems: native amylin clumps into amyloid fibrils, and the one approved analogue, pramlintide, lasts under an hour and has to be injected before every meal.
Cagrilintide is Novo Nordisk's answer. Its designers modified the amylin sequence for stability and attached a fatty acid so that it binds albumin and lasts long enough for a weekly injection. It activates both amylin receptors and the related calcitonin receptor, which is why it is described as a dual amylin and calcitonin receptor agonist. In obese mice, its weight-lowering effect depended on brain amylin receptors: removing RAMP1 and RAMP3, the proteins that turn calcitonin receptors into amylin receptors, blunted it.
On its own it was tested in a 26-week phase 2 trial in 706 adults with overweight or obesity. Weekly doses from 0.3 to 4.5 mg reduced weight by 6.0% to 10.8%, against 3.0% on placebo, and the top dose beat liraglutide 3.0 mg (10.8% against 9.0%). Gastrointestinal effects were more common than on placebo, mostly nausea.
Its main development path is as CagriSema, given together with semaglutide 2.4 mg. In REDEFINE 1, 3,417 adults with overweight or obesity lost 20.4% of body weight over 68 weeks on the combination against 3.0% on placebo; in a separate 68-week trial the combination beat semaglutide alone by 6.5 points (18.4% against 11.9%). In type 2 diabetes the combination lowered HbA1c slightly more than semaglutide alone in REIMAGINE 2, and in a smaller phase 2 trial cagrilintide alone lowered weight by 8.1% and HbA1c by 0.9 points over 32 weeks.
Cagrilintide is not approved anywhere, alone or in combination. CagriSema has been submitted to the FDA, as our pipeline coverage tracks; until a decision, the only lawful way to receive cagrilintide is in a clinical trial.
Mechanism of Action
Cagrilintide copies amylin, the fullness hormone released with insulin, and adds the stability and long life that native amylin lacks.
Amylin receptors in the brain
Amylin receptors are calcitonin receptors paired with RAMP proteins. In obese mice, removing RAMP1 and RAMP3 blunted cagrilintide's weight loss, pointing to brain amylin receptors as the main site of action.
Fullness and slower stomach emptying
Like natural amylin, it is designed to slow gastric emptying and reduce the after-meal glucagon rise, effects that lower food intake and after-meal glucose.
Lipidation for weekly dosing
A fatty acid side chain lets it bind albumin and avoids amylin's tendency to form fibrils, turning a hormone that lasts minutes into one injected weekly.
Complementing GLP-1
Amylin and GLP-1 act on overlapping but distinct appetite circuits; in trials, adding cagrilintide to semaglutide added weight loss beyond semaglutide alone.
Published Research
The studies behind cagrilintide, read from their PubMed abstracts.
Phase 2 dose-finding: 706 on cagrilintide
Over 26 weeks, weekly cagrilintide 0.3 to 4.5 mg reduced weight by 6.0% to 10.8% against 3.0% on placebo, and 4.5 mg beat liraglutide 3.0 mg (10.8% against 9.0%); gastrointestinal events affected 41% to 63% against 32%.
REDEFINE 1: with semaglutide, 3,417 adults
Over 68 weeks, weight fell 20.4% with cagrilintide-semaglutide against 3.0% on placebo (difference -17.3 points); gastrointestinal events affected 79.6% against 39.9%, mostly transient and mild to moderate.
REDEFINE 2: type 2 diabetes
In 1,206 adults with type 2 diabetes, weight fell 13.7% with cagrilintide-semaglutide against 3.4% on placebo over 68 weeks.
Phase 1b with semaglutide
In 96 participants, cagrilintide exposure rose in proportion to dose without changing semaglutide exposure; most adverse events were mild to moderate, 37% of them gastrointestinal.
Kidney and liver impairment
In 33 people with varying kidney function and 32 with varying liver function, single doses produced similar exposure across groups, with no consistent pattern by impairment.
How it was designed
Structure-activity work produced a stable, lipidated amylin analogue suitable for weekly dosing, addressing amylin's fibril formation and pramlintide's short half-life.
Brain amylin receptors
In obese mice, cagrilintide lowered body weight, and the loss of RAMP1 and RAMP3, which form amylin receptors 1 and 3, impeded its effect.
CagriSema against semaglutide alone: 331 adults
Over 68 weeks, weight fell 18.4% with cagrilintide-semaglutide against 11.9% with semaglutide alone (difference 6.5 points); gastrointestinal disorders affected 53% and 51%.
REIMAGINE 2: type 2 diabetes, 2,713 adults
HbA1c fell 1.91 points with cagrilintide-semaglutide 2.4 mg each against 1.75 with semaglutide 2.4 mg (difference 0.16, p=0.0035); the trial also included a cagrilintide-alone arm of 152 people.
Phase 2 in type 2 diabetes: 92 adults
Over 32 weeks, weight fell 15.6% with CagriSema, 5.1% with semaglutide and 8.1% with cagrilintide alone; HbA1c fell 2.2, 1.8 and 0.9 points.
Dosing Data
Cagrilintide has no approved dose. In trials it was injected under the skin once a week: from 0.3 to 4.5 mg alone in phase 2, and escalated to 2.4 mg alongside semaglutide 2.4 mg in the CagriSema trials.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
→ Blend & Stack Calculator — Cagrilintide is also sold in multi-peptide vials; the calculator shows what each draw delivers of every component; our blends and stacks hub sets out what each mix contains and what has been studied.
Side Effects & Contraindications
Reported Side Effects
From the trials above.
Contraindications & Cautions
Cagrilintide has no approved label. These cautions follow from the evidence.
Legal Status
Cagrilintide is investigational and not approved anywhere.
Frequently Asked Questions
?How much weight does cagrilintide cause on its own?
In a 26-week phase 2 trial, 6.0% to 10.8% depending on dose, against 3.0% on placebo.
?What is CagriSema?
Cagrilintide and semaglutide given together; in REDEFINE 1 the combination reduced weight by 20.4% over 68 weeks against 3.0% on placebo.
?Is cagrilintide approved?
No. It is investigational; FDA's Drugs@FDA database and EMA's register have no entry for it.
?Does cagrilintide work better with semaglutide?
Yes, in trials: over 68 weeks, the combination reduced weight by 18.4% against 11.9% with semaglutide alone.
?How is cagrilintide different from pramlintide?
Both copy amylin, but pramlintide lasts under an hour and is injected before meals, while cagrilintide is lipidated for once-weekly dosing.
?What are the side effects?
Mainly gastrointestinal, especially nausea: 41% to 63% on cagrilintide alone against 32% on placebo in phase 2.
References
- [fda] FDA. Drugs@FDA (openFDA): no application for cagrilintide. Read September 30, 2026.
- [other] European Medicines Agency. Medicines register: no entry for cagrilintide. Read September 30, 2026.
- [pubmed] Lau DCW, et al. "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." Lancet, 2021;398(10317):2160-2172. PMID: 34798060.
- [pubmed] Garvey WT, et al. "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity." N Engl J Med, 2025;393(7):635-647. PMID: 40544433.
- [pubmed] Davies MJ, et al. "Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes." N Engl J Med, 2025;393(7):648-659. PMID: 40544432.
- [pubmed] Enebo LB, et al. "Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial." Lancet, 2021;397(10286):1736-1748. PMID: 33894838.
- [pubmed] Nielsen MJF, et al. "Renal or Hepatic Impairment Does Not Affect Pharmacokinetics, Safety, or Tolerability of Subcutaneous Cagrilintide." Clin Pharmacokinet, 2026;65(7):1087-1099. PMID: 42228334.
- [pubmed] Kruse T, et al. "Development of Cagrilintide, a Long-Acting Amylin Analogue." J Med Chem, 2021;64(15):11183-11194. PMID: 34288673.
- [pubmed] Carvas AO, et al. "Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3." EBioMedicine, 2025;118:105836. PMID: 40609154.
- [pubmed] Yamauchi T, et al. "Efficacy and safety of co-administered cagrilintide and semaglutide versus semaglutide alone in adults with overweight or obesity with or without type 2 diabetes in Japan and Taiwan (REDEFINE 5): a multicentre, randomised, active-controlled, phase 3a trial." Lancet Diabetes Endocrinol, 2026;14(6):450-462. PMID: 42009015.
- [pubmed] Buse JB, et al. "Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study." Lancet Diabetes Endocrinol, 2026;14(8):662-677. PMID: 42251859.
- [pubmed] Frias JP, et al. "Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial." Lancet, 2023;402(10403):720-730. PMID: 37364590.
Sources & Citations
Every study on this page was read from its PubMed record. Regulatory status comes from FDA's Drugs@FDA database and EMA's register, read September 30, 2026. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.