AIM To examine the glucose-lowering mechanisms of the glucagon-like peptide-1 receptor agonist lixisenatide after two subsequent meals and in combination with basal insulin. MATERIALS AND METHODS Twenty-eight metformin-treated patients with type 2 diabetes were randomly assigned to treatment sequences with either lixisenatide or insulin glargine alone for 4 weeks, and a combination of both treatments for 4 weeks. Metabolic examinations were performed before and after each treatment period following breakfast and a late lunch 8 hours later. RESULTS Lixisenatide mainly reduced postprandial glycaemia, while insulin glargine mainly reduced fasting glucose after breakfast (P < 0.05). This was partially preserved after a late lunch (P < 0.05). After breakfast, lixisenatide reduced insulin secretion and glucagon levels significantly. These effects were lost after a late lunch. Insulin glargine did not significantly reduce glucagon or insulin secretion. Gastric emptying was slowed by lixisenatide, but not by insulin glargine after breakfast. After the late lunch, lixisenatide slightly accelerated gastric emptying. CONCLUSIONS Lixisenatide decelerates gastric emptying after breakfast, thereby reducing glycaemic excursions, insulin secretion and glucagon levels. The glycaemic reduction persists until after a late lunch, despite accelerated gastric emptying. The combination with insulin glargine enhances the glucose-lowering effect because of complementary modes of action.

中文翻译：

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依西拉肽，甘精胰岛素或其组合序贯治疗对2型糖尿病患者与餐相关的血糖波动，胰岛素和胰高血糖素分泌以及胃排空的影响。

目的研究在连续两次进餐后与基础胰岛素联合使用后，胰高血糖素样肽-1受体激动剂利西拉来的降糖机制。材料与方法28例接受二甲双胍治疗的2型糖尿病患者被随机分配为分别接受利西拉肽或甘精胰岛素治疗的疗程，共4周，两种治疗相结合，疗程为4周。在早餐后和每个小时的8小时后的午餐后的每个治疗阶段之前和之后进行代谢检查。结果利西拉来主要减少餐后血糖，而甘精胰岛素主要减少早餐后的空腹血糖（P <0.05）。午饭后部分保存（P <0.05）。早餐后，利西拉来可以显着降低胰岛素分泌和胰高血糖素水平。午饭后这些效果消失了。甘精胰岛素没有显着减少胰高血糖素或胰岛素的分泌。早餐后利西拉来可减缓胃排空，但甘精胰岛素不减缓胃排空。午饭后，利西拉来稍微加速了胃排空。结论早餐后利西拉来可减少胃排空，从而减少血糖波动，胰岛素分泌和胰高血糖素水平。尽管胃排空加快，但血糖降低一直持续到午餐后。由于互补的作用方式，与甘精胰岛素的组合可增强降糖效果。午饭后，利西拉来稍微加速了胃排空。结论早餐后利西拉来可减少胃排空，从而减少血糖波动，胰岛素分泌和胰高血糖素水平。尽管胃排空加快，但血糖降低一直持续到午餐后。由于互补的作用方式，与甘精胰岛素的组合可增强降糖效果。午饭后，利西拉来稍微加速了胃排空。结论早餐后利西拉来可减少胃排空，从而减少血糖波动，胰岛素分泌和胰高血糖素水平。尽管胃排空加快，但血糖降低一直持续到午餐后。由于互补的作用方式，与甘精胰岛素的组合可增强降糖效果。