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Peer review Peer review information Nature Medicine thanks Qiwei Li, Carel le Roux and Katherine Tuttle for their contribution to the peer review of this work
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
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The best approach is balanced: keep the metabolic benefits, understand the retinal risk, and monitor the eye appropriately
Questions to ask before restarting How long has it been since my last dose, and what does that mean for my restart assessment
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