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As a GLP-1 receptor agonist, semaglutide mimics the actions of endogenous GLP-1 but with one critical engineering advantage: while native GLP-1 has a biological half-life of only a few minutes before being cleaved by the enzyme DPP-4, semaglutide achieves a half-life of approximately seven days through structural modifications that include an Aib amino acid substitution at position 8 (blocking DPP-4 recognition) and a C18 fatty acid chain attached via a linker, which enables reversible binding to albumin in the bloodstream

Journal of Molecular Medicine