Cagrilintide (revision 4)
Old revision·13:29, 6 Sep 2024·SemaglutideSasha
| Cagrilintide | |
|---|---|
| Class | Amylin receptor agonist |
| Route | Subcutaneous, weekly |
| Status | Investigational; not approved alone |
| Combination | CagriSema with semaglutide |
| Compound infobox · conventions | |
Cagrilintide is a long-acting analogue of amylin, engineered to resist the aggregation that makes the native human sequence undevelopable and acylated for albumin binding so that weekly dosing is possible.[1]
Its actions follow those of amylin: slowed gastric emptying, suppression of postprandial glucagon, and reduced food intake through hindbrain circuits distinct from the GLP-1 pathway.[2]
Design
[edit]The engineering problem is the same one pramlintide solved differently. Human amylin forms fibrils at concentrations well below those a formulation requires, so a developable analogue must break the β-sheet propensity of the central region while retaining receptor activity.[2]
Cagrilintide adds acylation to that, giving the long half-life the earlier mealtime analogue lacked. It engages the calcitonin receptor as well as the amylin receptor complexes, and whether that broader engagement contributes to or detracts from the effect is not established.[1]
References
- ^ a b Lau DCW, Erichsen L, Francisco AM, et al. "Once-weekly cagrilintide for weight management in people with overweight and obesity." The Lancet 398(10317):2160–2172 (2021). PMID 34798060.
- ^ a b Hay DL, Chen S, Lutz TA, Parkes DG, Roth JD. "Amylin: pharmacology, physiology, and clinical potential." Pharmacological Reviews 67(3):564–600 (2015). PMID 26071095.