CEDAR

Scientific Reference

Cagrilintide (AM833)

Evidence profile: Human Phase 3 evidence

Cagrilintide (AM833) is a long-acting, lipidated amylin analog designed to activate both amylin and calcitonin receptors, producing potent effects on satiety and metabolic regulation. Developed for obesity and type 2 diabetes management, it has demonstrated substantial weight loss outcomes in clinical trials, particularly when combined with semaglutide (CagriSema). Its extended half-life and once-weekly dosing profile enable sustained appetite suppression and metabolic modulation. Phase 3 trials have shown significant reductions in body weight and improvements in glycemic control, positioning it as a next-generation therapy for metabolic disease.

Mechanism of Action

Cagrilintide acts as a dual agonist at amylin and calcitonin receptors, enhancing satiety signaling and reducing food intake. The lipidated structure prolongs circulation time, allowing sustained receptor activation. These effects lead to reduced caloric intake, improved metabolic regulation, and significant weight loss without direct stimulation of insulin secretion.

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

  • 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