Cagrilintide

How Cagrilintide is described to act.

Cagrilintide (AM833) is a lipidated, long-acting analogue of the pancreatic hormone amylin, engineered to resist the amyloid fibril formation that makes native amylin a difficult drug-design target. Pharmacological profiling across 25 endpoints in vitro characterised it as a non-selective agonist at amylin receptors, which are heterodimers of the calcitonin G protein-coupled receptor with receptor activity-modifying proteins, and which also independently activates the calcitonin receptor; this produces a binding and activation profile distinct from selective amylin receptor agonists such as pramlintide. Native amylin is described in this literature as a pancreatic hormone that induces satiety, with amylin receptor agonism discussed as complementary to GLP-1 receptor agonism. In rats, roughly one third of the weight loss produced by an amylin plus GLP-1 analogue combination was attributed to blunting of metabolic adaptation rather than to reduced energy intake alone.

Mechanistic descriptions summarize published in vitro and animal work. They are not a representation of efficacy or safety in any subject, and no administration guidance is given or implied.

Medicinal chemistry work described the structure-activity effort behind the selection of cagrilintide from a series of stable lipidated amylin analogues. A multicentre, randomised, double-blind, placebo- and active-controlled dose-finding phase 2 trial in adults with overweight or obesity and without diabetes assessed the dose-response relationship for change in bodyweight, safety and tolerability across a 26-week treatment period. A randomised, placebo-controlled phase 1b multiple-ascending-dose trial in otherwise healthy participants with a body-mass index of 27.0-39.9 kg/m2 took the number of treatment-emergent adverse events as its primary endpoint, with pharmacokinetic measures as secondary endpoints, when cagrilintide and semaglutide were co-administered. A 32-week phase 2 trial in adults with type 2 diabetes took change from baseline in glycated haemoglobin as the primary endpoint, with bodyweight, fasting plasma glucose and continuous glucose monitoring parameters as secondary endpoints. In rats, the combination reduced food intake and produced weight loss that pair-feeding did not fully reproduce, which the authors attributed to preserved energy expenditure.

Sources & references

Cited literature is provided for scientific reference only and does not constitute a representation of efficacy or safety in any subject. All research findings presented are sourced from peer-reviewed journals and are provided for educational reference only.

1. 01
   CagriSema drives weight loss in rats by reducing energy intake and preserving energy expenditure

   Jacobsen JM, et al. · Nat Metab, 2025

   PMID 40629149DOI 10.1038/s42255-025-01324-8

2. 02
   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

   Frias JP, et al. · Lancet, 2023

   PMID 37364590DOI 10.1016/S0140-6736(23)01163-7

3. 03
   Development of Cagrilintide, a Long-Acting Amylin Analogue

   Kruse T, et al. · J Med Chem, 2021

   PMID 34288673DOI 10.1021/acs.jmedchem.1c00565

4. 04
   AM833 Is a Novel Agonist of Calcitonin Family G Protein-Coupled Receptors: Pharmacological Comparison with Six Selective and Nonselective Agonists

   Fletcher MM, et al. · J Pharmacol Exp Ther, 2021

   PMID 33727283DOI 10.1124/jpet.121.000567

5. 05
   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, 2021

   PMID 34798060DOI 10.1016/S0140-6736(21)01751-7

6. 06
   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

   Enebo LB, et al. · Lancet, 2021

   PMID 33894838DOI 10.1016/S0140-6736(21)00845-X

Every entry links to its record at the publisher or on PubMed. Titles are reproduced exactly as published.