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.
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.
Where to get it
Verified directory — coming soon
PeptaHub is building a verified supplier directory with third-party testing data, compliance status, and reader ratings.