Lixisenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist that can be used in the treatment of type 2 diabetes mellitus (T2DM).
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Lixisenatide is a synthetic, potent and selective GLP-1 receptor agonist with Ki value of 1.33nM. It is used in the treatment for type 2 diabetes mellitus (T2DM) and suggests actions that are highly relevant to the long-term maintenance of glucose homeostasis. Lixisenatide is a 44 amino acid peptide and shares similar sequence with pharmacologically active forms of human GLP-1 or exendin-4. ZP10A demonstrated dose-dependent improvement of glucose tolerance with an ED50 value of 0.02 nmol/kg i.p. in an oral glucose tolerance test (OGTT) in diabetic db/db mice. Long-term stimulation by Lixisenatide at 10nM for 24h led increased level of Akt-phosphorylation in INS-1 cells. Lixisenatide at 10nM protected rat-derived β-cell line, Ins-1 cells, from both lipid- and cytokine-induced apoptosis. Also it prevented lipotoxicity-induced insulin depletion in human islets and preserved insulin production, storage and pancreatic β-cell function in vitro. Lixisenatide improved basal blood glucose and HbA1c with a rapid onset and sustained duration of action, and prevented the deterioration of pancreatic responsiveness and glucose homeostasis in animal models of diabetes. It delayed gastric emptying and reduced food intake.
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