What Is Cagrilintide? Definition and What Research Reports

Plain-language definition

Cagrilintide is a synthetic, long-acting version of a natural human hormone called amylin. Amylin is released by the pancreas at the same time as insulin whenever a person eats, and it acts on the brain to signal fullness and to slow how quickly the stomach empties. Native amylin breaks down and clumps together too quickly to be useful as a drug, so chemists redesigned the molecule so it stays stable and remains in circulation long enough for once-weekly dosing. Cagrilintide is that redesigned molecule. It has been investigated in clinical trials as a weight-management candidate, most prominently in combination with the GLP-1 receptor agonist semaglutide — a fixed-combination product referred to in the literature as CagriSema. This page is for educational purposes only and is not medical advice; consult a licensed physician for any health decision.

What cagrilintide is in biochemical terms

Cagrilintide is a 32–amino-acid peptide analogue of human amylin (also called islet amyloid polypeptide, or IAPP). Medicinal chemistry work describing its development explained that native human amylin is prone to fibrillation and has a very short half-life, and that the analogue was built by substituting residues to suppress aggregation and by attaching a lipid side chain that promotes reversible binding to albumin, which extends circulation time enough to support weekly administration (PMID 34288673). Reviews of the compound described it as a long-acting amylin analogue developed for the treatment of obesity (PMID 36883831).

Receptor biology

Amylin signalling is mediated by receptor complexes formed when the calcitonin receptor pairs with receptor activity-modifying proteins, producing the AMY1, AMY2 and AMY3 receptor subtypes. A 2025 preclinical study reported that cagrilintide lowered body weight through brain amylin receptors 1 and 3, implicating central rather than purely peripheral signalling in the weight effect (PMID 40609154). Cagrilintide is frequently described as a non-selective amylin analogue because it also engages calcitonin receptors, which distinguishes it from earlier amylin-based agents.

Regulatory framing

Cagrilintide has been studied under investigational protocols rather than as a long-marketed medicine, and material sold outside of licensed pharmaceutical channels is typically labelled "research use only" (RUO), meaning it is not authorised for human administration. Readers should note that regulatory status differs by jurisdiction and changes over time; nothing on this page describes approval status as a recommendation, and it is not legal advice.

How the term is used in peptide research

In the published literature, "cagrilintide" refers specifically to the single-molecule amylin analogue. Three usages appear most often:

• Cagrilintide monotherapy — the analogue studied on its own, as in the phase 2 dose-finding programme in overweight and obesity (PMID 34798060).
• Co-administered cagrilintide and semaglutide — two agents given together, as in the phase 1b multiple-dose study (PMID 33894838).
• CagriSema — the fixed-dose combination of cagrilintide with semaglutide evaluated in later-phase obesity and type 2 diabetes trials (PMID 40544433).

Where the term is misused

• Treating "cagrilintide" and "CagriSema" as synonyms. They are not: CagriSema contains semaglutide as well, and outcomes reported for the combination cannot be attributed to the amylin analogue alone.
• Calling it a GLP-1 agonist. Cagrilintide acts at amylin/calcitonin receptors, not the GLP-1 receptor; the pharmacology summarised in its development paper is distinct (PMID 34288673).
• Confusing it with pramlintide. Pramlintide is a separate, short-acting amylin analogue requiring multiple daily injections; cagrilintide was engineered for weekly administration (PMID 36883831).
• Describing grey-market research material as equivalent to trial drug. Published findings come from manufactured, characterised investigational product administered under supervision, not from unverified material.

Related terms

What the published literature reports

Cagrilintide alone

A multicentre, randomised, double-blind, placebo-controlled and active-controlled phase 2 dose-finding trial evaluated once-weekly cagrilintide in people with overweight and obesity. The study, published in 2021, tested a range of weekly doses against placebo and against the active comparator liraglutide 3.0 mg, and researchers reported greater body-weight reduction with cagrilintide than with placebo across the dose range studied (PMID 34798060). A narrative review of the compound summarised this programme and framed cagrilintide as a long-acting amylin analogue under development for obesity (PMID 36883831).

Combination with semaglutide

A randomised, controlled phase 1b trial examined multiple doses of cagrilintide given concomitantly with semaglutide 2.4 mg and reported on safety, tolerability, pharmacokinetics and pharmacodynamics of the pairing (PMID 33894838). A subsequent multicentre, randomised, double-blind, active-controlled phase 2 trial assessed once-weekly cagrilintide 2.4 mg co-administered with once-weekly semaglutide 2.4 mg in people with type 2 diabetes, where researchers reported efficacy and safety outcomes versus active comparators (PMID 37364590).

Larger 2025 trials extended this work. One reported outcomes for coadministered cagrilintide and semaglutide in adults with overweight or obesity (PMID 40544433), and a companion trial reported outcomes for cagrilintide–semaglutide in adults with overweight or obesity and type 2 diabetes (PMID 40544432). A phase 3 study, REIMAGINE 2, compared cagrilintide–semaglutide with semaglutide or cagrilintide alone in people with type 2 diabetes, providing a direct comparison of the combination against each component (PMID 42251859).

Pooled analyses and secondary outcomes

A systematic review and meta-analysis examined cagrilintide alone and in combination with semaglutide as anti-obesity medications and pooled the available randomised evidence (PMID 39676787). A later systematic review and meta-analysis with GRADE assessment compared CagriSema with semaglutide monotherapy or placebo for obesity (PMID 41759565). A secondary analysis of the REDEFINE 1 trial reported that CagriSema reduced blood pressure in adults with overweight or obesity (PMID 41328546).

Adverse Events: What Studies Report

Across the cagrilintide literature, gastrointestinal effects were the adverse events most commonly described. The phase 2 dose-finding trial in overweight and obesity reported that gastrointestinal events were the most frequent adverse events and were generally mild to moderate (PMID 34798060). The phase 1b study of cagrilintide with semaglutide 2.4 mg also assessed safety and tolerability of the co-administered regimen (PMID 33894838), and the phase 2 type 2 diabetes trial of cagrilintide 2.4 mg with semaglutide 2.4 mg reported safety alongside efficacy outcomes (PMID 37364590). Pooled safety data were examined in the 2024 systematic review and meta-analysis (PMID 39676787). Readers interested in exact event rates should consult the primary publications, since figures vary by dose, population and trial duration.

What the term does not mean

Cagrilintide is not a nutritional supplement, not an approved over-the-counter product, and not interchangeable with any GLP-1 medicine. Trial findings describe averaged group outcomes under monitored conditions with defined inclusion criteria; they do not describe what would happen to any individual. Nothing here is guidance on obtaining or administering any compound.

This page is for educational purposes only and is not medical advice; consult a licensed physician before making any health decision.

References

• Development of Cagrilintide, a Long-Acting Amylin Analogue (Journal of Medicinal Chemistry, 2021)
• 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)
• 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)
• 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)
• Cagrilintide: A Long-Acting Amylin Analog for the Treatment of Obesity (Cardiology in Review, 2024)
• Efficacy and Safety of Cagrilintide Alone and in Combination with Semaglutide (Cagrisema) as Anti-Obesity Medications: A Systematic Review and Meta-Analysis (Indian Journal of Endocrinology and Metabolism, 2024)
• Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (New England Journal of Medicine, 2025)
• Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (New England Journal of Medicine, 2025)
• Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3 (EBioMedicine, 2025)
• 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 & Endocrinology, 2026)
• CagriSema Versus Semaglutide Monotherapy or Placebo for Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with GRADE Assessment (American Journal of Cardiology, 2026)
• CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1 (Hypertension, 2026)