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PMID: 30529260

Structural and molecular differences include: Amino acid composition : Semaglutide contains specific substitutions that confer DPP-4 resistance, whereas native GLP-1 is rapidly cleaved by this ubiquitous enzyme Albumin binding : The fatty acid side chain attached to lysine at position 26 in semaglutide enables prolonged circulation through albumin binding, a property absent in natural GLP-1 Molecular stability : Structural modifications protect semaglutide from enzymatic degradation and renal clearance that rapidly eliminate native GLP-1 From a clinical perspective, natural GLP-1 cannot be administered as a therapeutic agent due to its extremely short half-life, which would require continuous intravenous infusion for sustained effect

(2011, February)