Cagrilintide: Mechanism, Research & UK Safety Profile
Also known as: AM833
Investigational long-acting amylin analogue under development for chronic weight management, principally in combination with semaglutide (CagriSema). Not licensed for human therapeutic use in the UK.
Molecular weight
Approx. 5.3 kDa
Half-life
Engineered for once-weekly dosing via albumin binding.
Category
Amylin analogue
Overview
Cagrilintide (AM833) is a once-weekly amylin analogue developed by Novo Nordisk. Amylin is a pancreatic peptide co-secreted with insulin that slows gastric emptying, suppresses postprandial glucagon and signals satiety via the area postrema. Cagrilintide is being studied as a complement to GLP-1 receptor agonism, with the integrated rationale that combining amylin and GLP-1 mechanisms produces additive weight-management benefit. The leading combination in development is CagriSema (cagrilintide + semaglutide). Cagrilintide is investigational and not licensed for human therapeutic use in the UK.
Discovery & Research History
Cagrilintide emerged from Novo Nordisk's amylin-analogue programme, building on the pharmacology of native human amylin and the earlier marketed analogue pramlintide. Phase 1 and phase 2 monotherapy weight studies established tolerability and dose-response. The combination programme with semaglutide (CagriSema) has progressed through phase 2 and into phase 3 evaluation across obesity and type 2 diabetes populations. Topline phase 3 results have evolved during the 2024-2026 readout cycle.
Mechanism of Action
Amylin signalling acts via the calcitonin receptor family with receptor activity modifying proteins (RAMPs), with key effects on the area postrema (satiety, nausea regulation), gastric emptying and glucagon suppression. Cagrilintide is a fatty-acid-acylated amylin analogue engineered for once-weekly half-life via albumin binding. The combined mechanism with GLP-1 receptor agonism is hypothesised to engage central appetite circuits through complementary pathways, with downstream effects on food intake and body weight.
Researched Effects
- Body-weight reduction in adults with overweight or obesity, in monotherapy and combination phase 2 trials.
- Additive weight-management effects when combined with semaglutide (CagriSema).
- Tolerability profile broadly consistent with the GI-class adverse-event pattern.
Theoretical Research Protocols
- Dosage range
- Trial-arm doses are research records. This page is not a prescribing or self-administration guide. See published primary trial reports for the relevant dosing arms.
- Frequency
- Once-weekly subcutaneous administration in pivotal trials.
- Duration
- 68-72 weeks in phase 3 obesity trials; longer-term data emerging.
- Administration routes
- Subcutaneous (clinical trial setting)
Safety Profile
Common side effects (research)
- Gastrointestinal events (nausea, vomiting, diarrhoea, constipation) consistent with the wider amylin / incretin class profile.
- Injection-site reactions (typically mild and transient).
Rare risks
- Severe GI events with dehydration risk.
- Pharmacovigilance for rare events is ongoing as a function of trial reporting.
Contraindications
- Investigational compound — eligibility is defined by the relevant clinical trial protocol.
- Pregnancy / breastfeeding are typical trial exclusions.
UK Regulatory Status
United Kingdom (MHRA): Investigational. Not MHRA-licensed for any human therapeutic indication.
European Union (EMA): Investigational. Not EMA-licensed at the time of review.
Notes: Cagrilintide is investigational across all major jurisdictions at the time of review. Use is restricted to authorised, ethically approved clinical research.
Related research resources
Key Research Studies
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. Lancet 2021.
Phase 1b study establishing safety and tolerability of CagriSema combination across a dose range, with body-weight reduction reported in excess of semaglutide alone in the studied cohort.
Read sourceNovo Nordisk REDEFINE 1 and 2 programme — phase 3 trials of CagriSema across obesity and type 2 diabetes
Phase 3 evaluation of CagriSema vs comparator arms across obesity and type 2 diabetes populations. Topline phase 3 readouts have evolved during the 2024-2026 cycle; refer to current ClinicalTrials.gov records and primary publications for current results.
Frequently Asked Questions
What is cagrilintide?
An investigational long-acting amylin analogue developed by Novo Nordisk, studied principally in combination with semaglutide (CagriSema) for chronic weight management. Not licensed for human therapeutic use in the UK.
Is cagrilintide available in the UK?
No. Cagrilintide is investigational and is not licensed by the MHRA for any human therapeutic indication. Use outside an authorised clinical trial is not lawful.
How is cagrilintide different from a GLP-1 receptor agonist?
Cagrilintide acts on amylin pathways; GLP-1 receptor agonists act on the GLP-1 receptor. The combined CagriSema therapy hypothesises additive weight-management benefit from engaging both mechanisms.
Related trials
No published trials yet linked to this page. Source verification required.