Cobalt PeptidesResearch Grade

Scientific Reference

Cagrilintide (AM833)

Evidence profile: Human Phase 3 evidence

Cagrilintide is a synthetic, lipidated analogue of amylin, a 37-residue peptide hormone released alongside insulin from pancreatic beta cells. Native human amylin aggregates readily and is short-lived in circulation, so analogues for research have been engineered for stability. Cagrilintide carries a fatty-acid side chain that binds albumin in the blood, lengthening its half-life in pharmacokinetic studies. It is described as acting at both amylin receptors and the calcitonin receptor. After animal work it entered human clinical trials in metabolic research, examined both on its own and together with a GLP-1 receptor agonist. Compared with amylin itself, the published pharmacology of this analogue is recent and narrow.

Mechanism of Action

Amylin receptors form 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 these amylin receptor complexes and the calcitonin receptor on its own, hence its description as a non-selective amylin and calcitonin receptor agonist. Both receptor types couple mainly to Gs and cAMP signalling. In animal studies, amylin's own actions have been mapped largely to the area postrema and related hindbrain regions, which are studied in the control of feeding and gastric emptying. Binding of the lipid chain to albumin slows clearance.

Molecular Information

  • Type: Lipidated amylin analog
  • Length: 37 amino acids
  • 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

  • Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes

    Davies MJ et al. · The New England journal of medicine · 2025 · Clinical

    PMID 40544432 — View on PubMed