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10.1146/annurev.py.33.090195.001503 9 BarnaB.ÁdámA.KirályZ

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Metabolism & Elimination The metabolic fate of both components involves proteolytic degradation and renal clearance [19]: GLP3 contains DPP-4 resistant modifications (Aib2 residue) providing enzymatic stability Cagrilintide incorporates proline residues reducing fibril formation and improving stability Both peptides undergo gradual proteolytic cleavage to smaller peptide fragments Renal elimination represents the primary excretion pathway for metabolites No significant hepatic metabolism through cytochrome P450 pathways Steady-state concentrations are achieved after 4-5 weeks of once-weekly dosing for both components, with minimal accumulation beyond expected levels based on half-life calculations

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