Pharmacodynamics of the glucagon-like peptide-1 receptor agonist lixisenatide in Japanese and Caucasian patients with type 2 diabetes mellitus poorly controlled on sulphonylureas with/without metformin

Aims: The PDY6797 study evaluated efficacy, safety and pharmacodynamics of lixisenatide in Japanese and Caucasian patients with type 2 diabetes mellitus (T2DM) insufficiently controlled with sulphonylureas with/without metformin. Methods: This randomized, double-blind, placebo-controlled trial comprised a single-dose assessment of lixisenatide 5 and 10 g, and a 5to 6-week repeated dose-escalation assessment of lixisenatide 5 to 30 g once (QD) or twice daily (BID). The primary endpoint was change in postprandial plasma glucose (PPG) area under the curve (AUC)[0: 29-4: 30 h] after a standardized breakfast at the highest tolerated lixisenatide dose. Change from baseline in glycated haemoglobin (HbA1c), 2-h PPG and fasting plasma glucose (FPG) were assessed, as were adverse events. Results: Change from baseline in PPG AUC[0: 29-4: 30 h] with lixisenatide QD and BID was significantly greater than placebo (p< 0.0001 for all study populations), with particularly prominent effects in Japanese patients. Greater reductions in PPG AUC[0: 29-4: 30 h] were seen with lixisenatide QD versus BID, while the totality of evidence suggested that the lixisenatide 20 g dose was optimal. In the overall population, changes from baseline for 2-h PPG, HbA1c and FPG were significant with lixisenatide QD and BID versus placebo (p< 0.01 for all). Lixisenatide was well tolerated. Conclusions: Lixisenatide significantly reduced PPG AUC[0: 29-4: 30 h] versus placebo at the highest well-tolerated dose in patients with T2DM treated with sulphonylureas with/ without metformin and had a good safety and tolerability profile. Japanese patients experienced particular benefits with lixisenatide in terms of reductions in PPG excursions.