Efficacy and safety of lixisenatide in the treatment of Type 2 diabetes mellitus: a review of Phase III clinical data.

Lixisenatide is a novel glucagon-like peptide-1 receptor agonist developed for the treatment of Type 2 diabetes mellitus (T2DM). In its clinical development program, once-daily lixisenatide has been associated with significant improvements in HbA (change from baseline to week 24: up to -0.92%) and postprandial plasma glucose (PPG; change from baseline to week 24 as add-on to basal insulin: up to -7.96 mmol/l) with beneficial weight effects (change from baseline to week 24: up to -2.0 kg as add-on to oral antidiabetic agents and -1.8 kg as add-on to basal insulin) and a low incidence of severe hypoglycemia (from 0 to 1.2% over 24 weeks). Pharmacodynamic data highlight differences between lixisenatide and other glucagon-like peptide-1 receptor agonists, demonstrating more pronounced effects on PPG than liraglutide, with less frequent dosing and a better tolerability profile than exenatide. Lixisenatide has recently been evaluated in a comprehensive Phase III clinical trial program in patients with T2DM, which included three large-scale studies of once-daily lixisenatide in combination with basal insulin. Lixisenatide has been studied as a monotherapy or oral agent combination, or with insulin. It may become a treatment option for certain patient groups in the near future, including those that are unable to reach target HbA goals despite treatment with basal insulin and a fairly well-controlled fasting plasma glucose, indicating that additional PPG control could be needed. This article reviews clinical data for lixisenatide to date, both as monotherapy and in combination with basal insulin, and discusses the implications of lixisenatide for the management of T2DM.