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Regul Pept. 2010 Sep 24;164(2-3):58-64. doi: 10.1016/j.regpep.2010.05.008. Epub 2010 Jun 2.

Pharmacological profile of lixisenatide: A new GLP-1 receptor agonist for the treatment of type 2 diabetes.

Author information

1
Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany. ulrich.werner@sanofi-aventis.com

Abstract

The glucagon-like peptide-1 (GLP-1) receptor represents an established therapeutic target in type 2 diabetes mellitus (T2DM). Agents that activate this receptor improve glucose tolerance alongside a low risk of hypoglycaemia, and have the potential to modify disease progression. Lixisenatide is a new potent and selective GLP-1 receptor agonist currently in development. The preclinical pharmacological profile of Lixisenatide suggests actions that are highly relevant to the long-term maintenance of glucose homeostasis. Lixisenatide protected Ins-1 cells (a rat-derived beta-cell line) from both lipid- and cytokine-induced apoptosis. More importantly, Lixisenatide also prevented lipotoxicity-induced insulin depletion in human islets and preserved insulin production, storage and pancreatic beta-cell function in vitro. Enhancement of insulin biosynthesis and pancreatic beta-cell volume could also be demonstrated in animal models of type 2 diabetes. The improvement of glucose-stimulated insulin secretion provided by Lixisenatide occurred in a strictly glucose-dependent manner. In animal models of diabetes, Lixisenatide improved basal blood glucose and HbA(1c) with a rapid onset and sustained duration of action, and prevented the deterioration of pancreatic responsiveness and glucose homeostasis. Lixisenatide also delayed gastric emptying and reduced food intake. The efficacy/safety profile of Lixisenatide is currently being studied further in an extensive ongoing Phase III clinical study programme. This article reviews the preclinical pharmacological profile of Lixisenatide.

PMID:
20570597
DOI:
10.1016/j.regpep.2010.05.008
[Indexed for MEDLINE]

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