Lixisenatide as add-on therapy to basal insulin

Abstract

Many patients with type 2 diabetes mellitus do not achieve target glycosylated hemoglobin A_1c levels despite optimally titrated basal insulin and satisfactory fasting plasma glucose levels. Current evidence suggests that HbA_1c levels are dictated by both basal glucose and postprandial glucose levels. This has led to a consensus that postprandial glucose excursions contribute to poor glycemic control in these patients. Lixisenatide is a once-daily, prandial glucagon-like peptide 1 (GLP-1) receptor agonist with a four-fold affinity for the GLP-1 receptor compared with native GLP-1. Importantly, lixisenatide causes a significant delay in gastric emptying time, an important determinant of the once-daily dosing regimen. An exendin-4 mimetic with six lysine residues removed at the C-terminal, lixisenatide has pronounced postprandial glucose-lowering effects, making it a novel incretin agent for use in combination with optimally titrated basal insulin. Lixisenatide exerts profound effects on postprandial glucose through established mechanisms of glucose-dependent insulin secretion and glucagon suppression in combination with delayed gastric emptying. This review discusses the likely place that lixisenatide will occupy in clinical practice, given its profound effects on postprandial glucose and potential to reduce glycemic variability.

Keywords:

• lixisenatide
• add-on therapy
• insulin
• GLP-1 receptor agonist
• postprandial glucose
• pharmacodynamics

Disclosure

Production of this paper was supported by Sanofi, which provided a grant and also checked the content for technical accuracy. ME has previously received consulting fees for advisory board participation with Sanofi. The authors report no other conflicts of interest in this work.