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Semaglutide emerged from Novo Nordisks systematic GLP-1 analogue optimisation programme as the successor to liraglutide , incorporating structural modifications addressing the three principal pharmacokinetic vulnerabilities of native GLP-1: DPP-IV susceptibility at position 8 addressed by Aib8 alpha-aminoisobutyric acid substitution, proteolytic cleavage at position 34 addressed by Arg34Lys substitution, and the short half-life of unmodified GLP-1 analogues addressed by the C18 fatty diacid conjugation providing tighter albumin binding and longer half-life than liraglutides C16 fatty acid, producing the approximately one-week half-life enabling once-weekly subcutaneous administration

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GLP-1 receptor agonists in delirium and encephalopathies: a neuroprotective scoping review

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