What Is Cagriniltide?
Quick Answer
Research Overview Cagriniltide (AM833/NN1213) is a long-acting acylated analogue of human amylin — a 37-amino acid pancreatic hormone co-secreted with insulin that regulates satiety and glucose homeostasis. Native human amylin is unstable, prone to amyloid fibril formation, and has a very short half...
Research Overview
Cagriniltide (AM833/NN1213) is a long-acting acylated analogue of human amylin — a 37-amino acid pancreatic hormone co-secreted with insulin that regulates satiety and glucose homeostasis. Native human amylin is unstable, prone to amyloid fibril formation, and has a very short half-life. The first-generation analogue, pramlintide, requires multiple daily injections.[2]
Cagriniltide overcomes these limitations through C20 fatty diacid acylation (via γ-glutamic acid spacer at Lysine 1), which binds serum albumin, extending the half-life to 159–195 hours and enabling once-weekly dosing. Proline substitutions (Pro21, Pro27) and specific amino acid changes (N14E, V17R) prevent fibril formation and stabilize the peptide's alpha-helix.[3]
The primary therapeutic strategy involves co-administration with semaglutide (branded as CagriSema). While GLP-1 agonists target incretin pathways, cagriniltide targets distinct amylin and calcitonin receptors in the hindbrain, activating non-overlapping satiety pathways for synergistic weight loss of up to 22.7% — significantly exceeding either monotherapy.[5][11]
References
- 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: a randomised, controlled, phase 1b trial. Lancet, 397(10286), 1736-1748, 2021.
- Lau DCW, et al. 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, 398(10317), 2160-2172, 2021.
- Kruse T, et al. Development of Cagrilintide, a Long-Acting Amylin Analogue. Journal of Medicinal Chemistry, 64(15), 11183-11194, 2021.
- Frias JP, et al. 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, 402(10403), 720-730, 2023.
- Garvey WT, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine, 393(7), 635-647, 2025.
- Davies MJ, et al. Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. New England Journal of Medicine, 393(7), 648-659, 2025.
- Verma S, et al. CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1. Hypertension, 83(2), e26055, 2026.
- Carvas AO, et al. Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3. EBioMedicine, 118, 105836, 2025.
- Cao J, et al. Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors. Nature Communications, 16, 3389, 2025.
- Gu YM, et al. Structural and mechanistic insights into dual activation of cagrilintide in amylin and calcitonin receptors. Acta Pharmacologica Sinica, 47(1), 162-172, 2026.
- Wang Y, Feng Z, Yu L. The next frontier in metabolic health: Cagrilintide-Semaglutide and the evolving landscape of therapies. The Innovation Medicine, 3(3), 100150, 2025.
- Fletcher MM, et al. AM833 Is a Novel Agonist of Calcitonin Family G Protein-Coupled Receptors: Pharmacological Comparison with Six Selective and Nonselective Agonists. JPET, 377(3), 417-440, 2021.
- Dahl K, et al. NN1213 – A Potent, Long-Acting, and Selective Analog of Human Amylin. Journal of Medicinal Chemistry, 67(14), 11688–11700, 2024.
- Becerril S, Frühbeck G. Cagrilintide plus semaglutide for obesity management. Lancet, 397(10286), 1687-1689, 2021.
- D'Ascanio AM, et al. Cagrilintide: A Long-Acting Amylin Analog for the Treatment of Obesity. Cardiology in Review, 32(1), 83-90, 2024.
- Mikhail N, Wali S. Cagrilintide Combined with Semaglutide: A New Approach for Treatment of Obesity and Type 2 Diabetes. Clinical Trials and Clinical Research, 2(5), 2023.
- Hales CM. Expanding the Treat-to-Target Toolbox for Obesity and Diabetes Care. New England Journal of Medicine, 393(7), 712-714, 2025.
- Gadde KM, Allison DB. Long-acting amylin analogue for weight reduction. Lancet, 398(10317), 2132-2134, 2021.
- Dehestani B, et al. Amylin as a Future Obesity Treatment. Journal of Obesity & Metabolic Syndrome, 30(4), 320-325, 2021.
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