Lixisenatide

Lixisenatide is a 44-amino acid synthetic peptide and a short-acting glucagon-like peptide-1 (GLP-1) receptor agonist. It is derived from exendin-4, a naturally occurring GLP-1 receptor agonist isolated from the venom of the Gila monster lizard (Heloderma suspectum), with two key structural modifications: deletion of proline at position 38 and addition of six lysine residues at the C-terminus. These modifications enhance resistance to enzymatic degradation by dipeptidyl peptidase-4 (DPP-4) and other proteases, extending the half-life to approximately 3 hours and enabling once-daily dosing. Lixisenatide selectively binds to the GLP-1 receptor with high affinity (IC50 = 1.4 nM), stimulating glucose-dependent insulin secretion and suppressing glucagon release.