Effects of lixisenatide once daily on gastric emptying in type 2 diabetes - Relationship to postprandial glycemia

Objectives: To determine the effects of lixisenatide, a new once-daily (QD) glucagon-like peptide-1 receptor agonist, on postprandial glucose (PPG) and gastric emptying, and the relationship between these effects in patients with type 2 diabetes mellitus (T2DM). Methods: Data were obtained from a randomized, double-blind, placebo-controlled, parallel-group study with treatment duration of 28 days in patients with T2DM receiving <= 2 oral antidiabetic drugs. Lixisenatide was injected subcutaneously using an ascending dose range (5-20 mu g) increased every fifth day in increments of 2.5 mu g. Blood glucose was determined before and after three standardized meals (breakfast, lunch, and dinner). Gastric emptying of the standardized breakfast was determined by a C-13-octanoic acid breath test at baseline (Day-1) and at Day 28. Results: A total of 21 and 22 patients were randomized to lixisenatide 20 mu g QD and placebo, respectively. With lixisenatide 20 mu g QD, there was a reduction in PPG when compared with placebo after breakfast (p < 0.0001), lunch (p < 0.001) and dinner (p < 0.05). Hence, lixisenatide 20 mu g administered in the morning exhibited a pharmacodynamic effect on blood glucose throughout the day. Gastric emptying (50% emptying time) increased substantially from baseline with lixisenatide 20 mu g QD, but not with placebo (change from baseline +/- SD: -24.1 +/- 133.1 min for placebo and 211.5 +/- 278.5 min for lixisenatide; p < 0.01). There was an inverse relationship, between PPG area under the curve after breakfast and gastric emptying with lixisenatide 20 mu g QD (n = 17, r(2) = 0.51, p < 0.05), but not with placebo. Conclusions: In this study, lixisenatide at a dose of 20 mu g QD reduced postprandial glycemic excursions in patients with T2DM, possibly as a result of sustained slowing of gastric emptying. (C) 2013 Elsevier B.V. All rights reserved.