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nominal concentration 4 mg per pen Three structural modifications distinguish semaglutide from native GLP-1: Aib (-aminoisobutyric acid) replacing alanine at position 8 (proglucagon numbering) increases the molecules resistance to degradation by DPP-4 Acylation of Lys via a Glu-2xOEG linker with octadecanedioic acid (C18 diacid) mediates reversible binding to serum albumin, extending the half-life by an order of magnitude Substitution Lys Arg eliminates a competing acylation site and additionally introduces resistance to NEP Structure and physicochemical properties Acylation of Lys is the central modification from a pharmacokinetic perspective