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doi: 10.1038/s41574-019-0311-6 109 WuF.GuoX.ZhangJ.ZhangM.OuZ.PengY

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Following subcutaneous administration in clinical models: Both components demonstrate prolonged absorption with peak plasma concentrations occurring 24-72 hours post-injection GLP3 exhibits approximately 6-day half-life enabling once-weekly dosing Cagrilintide demonstrates 120-165 hour half-life (5-7 days) suitable for weekly administration Lipid conjugation of both peptides enables albumin binding and extended systemic circulation Distribution patterns show systemic exposure with concentration in metabolically active tissues The fatty diacid modifications on both peptides (C20 for GLP3 , eicosanedioic acid for cagrilintide) serve as albumin-binding moieties that dramatically extend plasma residence time compared to native peptides

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