Cagrilintide (revision 13)
Old revision·22:44, 5 Feb 2025·INN_Ingrid
| CagrilintideInvestigational | |
|---|---|
| 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]
It is studied principally in combination with semaglutide as CagriSema, on the rationale that the two satiety mechanisms are additive. It is not approved for use in any indication.[1]
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]
Because the receptor family is unrelated to the incretin receptors, no single molecule can engage both; this is why the semaglutide combination is a co-formulation rather than a unimolecular dual agonist. See Dual incretin agonist.[2]
Reported findings
[edit]A phase 2 monotherapy trial reported approximately 10% weight reduction at 26 weeks. In combination with semaglutide the reported reduction exceeds that of either component alone; the combination programme is covered at CagriSema.[1]
Gastrointestinal adverse events dominate, as with the incretin agonists, and are concentrated during escalation. Whether combining two agents that both delay gastric emptying compounds them is addressed only indirectly by the published designs.[2]
No cardiovascular or other outcome evidence exists for this compound.[1]
See also
References
- ^ a b c d e 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 c d 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.