DRPSHP

Scientific Reference

Cagrilintide (AM833)

Evidence profile: Human Phase 3 evidence

Native human amylin is a poor research tool: the 37-residue hormone that pancreatic beta cells release alongside insulin aggregates readily and does not last long in circulation. Analogues are engineered to get round both problems, and Cagrilintide is one of them — a synthetic amylin analogue carrying a fatty-acid side chain that binds albumin in blood, which lengthened its half-life in pharmacokinetic studies. It is described as acting at amylin receptors and at the calcitonin receptor. Animal work was followed by human clinical trials in metabolic research, both of the compound alone and alongside a GLP-1 receptor agonist. Set against the literature on amylin itself, the published pharmacology of this analogue is recent and narrow.

Mechanism of Action

An amylin receptor is not a single protein. It forms when the calcitonin receptor, a class B G protein-coupled receptor, pairs with one of three receptor activity-modifying proteins — RAMP1, RAMP2 or RAMP3. Cagrilintide has been reported to activate those complexes and the calcitonin receptor on its own, which is why it is described as a non-selective amylin and calcitonin receptor agonist. Both receptor types couple mainly to Gs and cAMP. Amylin's own actions in animal studies have been mapped largely to the area postrema and neighbouring hindbrain regions, which is where work on feeding and gastric emptying concentrates. The albumin binding of the lipid chain is what slows clearance.

Molecular Information

  • Type: Lipidated amylin analogue
  • Molecular weight: 4409 g/mol
  • Molecular formula: C194H312N54O59S2
  • CAS: 1415456-99-3

Pharmacokinetics

The geometric mean of the t1/2 of cagrilintide in the renal function groups was 186 h for people with normal renal function (range 149-244 h)"; and in the hepatic study "ranging from 174 h (range 144-204 h) in the group with normal hepat… Median tmax 72 h (normal renal function, 0.6 mg SC monotherapy) and 45 h (normal hepatic function, 0.9 mg SC monotherapy). Lancet phase 1b: "Cagrilintide 0.16-4.5 mg had a half-life of 159-195 h, with a median tmax of 24-72 h.

Published Research

  • REDEFINE 1

    Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity

    Garvey WT et al. · The New England journal of medicine · 2025 · Clinical

    PMID 40544433 — View on PubMed

  • 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

    Lau DCW et al. · Lancet (London, England) · 2021 · Clinical

    PMID 34798060 — View on PubMed

  • 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

    Yamauchi T et al. · The lancet. Diabetes & endocrinology · 2026 · Clinical

    PMID 42009015 — View on PubMed

  • Cagrilintide-semaglutide (CagriSema) as an add-on to basal insulin in adults with type 2 diabetes (REIMAGINE 3): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study

    Rosenstock J et al. · Lancet (London, England) · 2026 · Clinical

    PMID 42251856 — View on PubMed

  • Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study

    Buse JB et al. · The lancet. Diabetes & endocrinology · 2026 · Clinical

    PMID 42251859 — View on PubMed

  • Efficacy and safety of zalfermin co-administered with semaglutide in participants with fibrosis and cirrhosis due to metabolic dysfunction-associated steatohepatitis: a phase 2, dose-ranging, double-blind, randomised controlled trial

    Loomba R et al. · The lancet. Gastroenterology & hepatology · 2026 · Clinical

    PMID 42456707 — View on PubMed