CagriSema (revision 4)
Old revision·23:55, 10 Nov 2024·DulaglutideDug
| CagriSema | |
|---|---|
| Components | Cagrilintide and Semaglutide |
| Form | Fixed-ratio co-formulation, single injection |
| Route | Subcutaneous, weekly |
| Status | Phase 3; not approved |
| Compound infobox · conventions | |
CagriSema is an investigational fixed-ratio combination of the amylin analogue cagrilintide and the GLP-1 receptor agonist semaglutide, co-formulated for weekly subcutaneous administration in a single injection. It is not approved for use in any indication.[1]
It differs architecturally from the unimolecular dual agonists: rather than one peptide engaging two receptors, CagriSema is two peptides in one syringe. The ratio is therefore set at formulation rather than by chemistry, and the two components retain their own pharmacokinetics — an advantage for design flexibility and a complication for exposure matching.[2]
Rationale
[edit]Amylin acts principally at the area postrema through calcitonin-receptor complexes; GLP-1 acts at the area postrema and at hypothalamic arcuate circuits through the GLP-1 receptor. The pathways converge on food intake but are pharmacologically separable, and preclinical work indicated additivity rather than redundancy.[2]
Both components also slow gastric emptying, which is where the mechanisms overlap most and where the tolerability cost of combining them is expected to concentrate.
References
- ^ Frías JP, Deenadayalan S, Erichsen L, 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." The Lancet 402(10403):720–730 (2023). PMID 37364590.
- ^ 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.