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Downstream effects via the active metabolite Pro-Gly-Pro, BDNF and NGF mRNA upregulation, and enkephalinase inhibition persist for 12 to 24 hours, which is why dosing frequency is set by downstream windows rather than plasma kinetics

The cagrilintide semaglutide combo has been investigated for dual engagement of amylin and GLP-1 signaling pathways

One example escalation schedule observed in Phase 2 obesity trials proceeded broadly as follows: Weeks 14: 2 mg once weekly (initiation phase) Weeks 58: 4 mg once weekly Weeks 912: 8 mg once weekly Weeks 13 onwards: Up to 12 mg once weekly (the maximum dose explored in Phase 2 trials) This is an illustrative example only

Chen, L., et al

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