Quick summary
Cagrilintide is a long-acting once-weekly amylin analog developed by Novo Nordisk for obesity treatment. In combination with semaglutide as CagriSema, Phase 3 trials showed 22.7% mean weight loss at 68 weeks, exceeding semaglutide alone at 14.8%.
Overview
Cagrilintide is a long-acting synthetic amylin analog developed by Novo Nordisk, designed for once-weekly subcutaneous dosing. It is built on a 37-amino acid pramlintide-like backbone with three key amino acid substitutions and N-terminal acylation with a fatty diacid chain, extending its half-life to approximately 7–8 days. It is being investigated as monotherapy for obesity and in combination with semaglutide as CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg) for substantially enhanced weight loss.
Mechanism of action
Cagrilintide activates the amylin receptor complex — calcitonin receptor (CTR) heterodimerized with receptor activity-modifying proteins RAMP1, RAMP2, and RAMP3 — expressed in the area postrema and nucleus tractus solitarius of the brainstem. Three key structural modifications enable its long action: N14E and V17R substitutions improve metabolic stability, P37Y provides additional protease resistance, and N-terminal acylation with a C20 eicosanedioic fatty diacid via gamma-glutamic acid linker enables albumin binding that extends circulation half-life. Amylin receptor activation produces satiety signaling (reducing meal size through AP/NTS neuronal pathways), slowing of gastric emptying via vagal efferent modulation, and suppression of post-prandial glucagon from pancreatic alpha cells. The CagriSema combination exploits complementary and partially non-overlapping neural circuits — amylin receptors act on different brainstem nuclei than GLP-1 receptors — producing additive weight loss exceeding either agent alone.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| Obesity treatment (clinical trial protocol) | subcutaneous | 0.25–2.4 mg | once weekly | In REDEFINE trials: stepwise dose escalation from 0.25 mg/week, increasing every 4 weeks to maintenance dose of 2.4 mg/week. Titration reduces nausea incidence. |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
Phase 2 CALM trial demonstrated cagrilintide monotherapy reduces body weight by 10.8% at 26 weeks (highest 4.5 mg dose) versus 3.0% placebo. The REDEFINE 1 Phase 3 trial of CagriSema showed 22.7% mean weight loss at 68 weeks in adults with obesity, exceeding semaglutide-alone (14.8%) in parallel trials. Cagrilintide's tolerability profile is consistent with the amylin class — nausea is the primary adverse event, with severity lower than pramlintide due to slower absorption. Cardiovascular outcome data are pending. No FDA approval has been granted as of 2026; regulatory submission is anticipated following completion of Phase 3 REDEFINE studies.[1][2][3][4]
Evidence grading
Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.
Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with Cagrilintide for synergistic effects.
Legal status
Investigational drug under active Phase 3 development by Novo Nordisk. Not FDA-approved as of 2026. Not available through commercial or compounding channels in the US. Available only through sponsored clinical trials. CAS: 1415456-99-3.
Sourcing & access
Research compound
Cagrilintide is classified as a research compound. Regulatory status varies by jurisdiction. Always verify current legal status and source from vendors providing third-party certificates of analysis (COA).
Frequently asked questions
Cagrilintide (AM833) is a long-acting synthetic amylin analog with a half-life of approximately 7-8 days, enabling once-weekly dosing. It is developed by Novo Nordisk and is being investigated both as monotherapy and in combination with semaglutide as CagriSema.
Cagrilintide activates the amylin receptor complex in the brainstem, producing satiety signaling that reduces meal size, slowing gastric emptying, and suppressing post-prandial glucagon. The CagriSema combination exploits complementary amylin and GLP-1 neural circuits for additive weight loss.
Phase 3 trials show nausea as the primary adverse event (mild to moderate, dose-dependent), along with vomiting, diarrhea, decreased appetite, injection site reactions, fatigue, and headache. It is not FDA-approved as of 2026 and is available only through clinical trials.
CagriSema is the combination of cagrilintide 2.4 mg plus semaglutide 2.4 mg given once weekly. The REDEFINE 1 Phase 3 trial showed 22.7% mean weight loss at 68 weeks, significantly exceeding the 14.8% achieved by semaglutide alone.
Research references
- 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
- 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 trialPubMed
- Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)PubMed
- Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2)PubMed