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10.1007/s12020-018-1708-z 31 LingvayI.BauerR.Baker-KnightJ.LawsonJ.PratleyR

Metabolism & Elimination Both peptides undergo similar metabolic pathways despite their structural differences: GLP1 metabolism: Proteolytic cleavage of the peptide backbone across multiple tissues Sequential beta-oxidation of the fatty acid side chain No organ-specific metabolism with degradation occurring in multiple tissues simultaneously Six identified metabolites in human plasma, with metabolite P3 comprising approximately 7.7% of circulating drug-related material Intact peptide predominance with 69-83% of circulating material remaining as intact GLP1 Cagrilintide metabolism: Similar proteolytic pathways to GLP1 due to peptide structure Fatty acid chain processing through beta-oxidation mechanisms Albumin-mediated protection reducing enzymatic access to the peptide backbone Reversible albumin binding allowing gradual release and metabolism No specific organ predominance for metabolic clearance The remarkably similar half-lives of both peptides (159-195 hours for cagrilintide, 145-165 hours for GLP1) enable synchronized pharmacokinetic profiles ideal for fixed-dose combination therapy

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