Corresponding author: Julio Rosenstock,
Diabetes Care. 2013 Oct;36(10):2945-51. doi: 10.2337/dc12-2709. Epub 2013 May 22.
To compare efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled with metformin.
Adults with diabetes inadequately controlled (HbA1c 7-10%) with metformin were randomized to lixisenatide 20 μg once daily (n=318) or exenatide 10 μg twice daily (n=316) in a 24-week (main period), open-label, parallel-group, multicenter study. The primary objective was a noninferiority assessment of lixisenatide versus exenatide in HbA1c change from baseline to week 24.
Lixisenatide once daily demonstrated noninferiority in HbA1c reduction versus exenatide twice daily. The least squares mean change was -0.79% (mean decrease 7.97 to 7.17%) for lixisenatide versus -0.96% (mean decrease 7.96 to 7.01%) for exenatide, and treatment difference was 0.17% (95% CI, 0.033-0.297), meeting a predefined noninferiority upper CI margin of 0.4%. Responder rate (HbA1c<7.0%) and improvements in fasting plasma glucose were comparable. Both agents induced weight loss (from 94.5 to 91.7 kg and from 96.7 to 92.9 kg with lixisenatide and exenatide, respectively). Incidence of adverse events (AEs) was similar for lixisenatide and exenatide, as was incidence of serious AEs (2.8 and 2.2%, respectively). Discontinuations attributable to AEs occurred in 33 lixisenatide (10.4%) and 41 exenatide (13.0%) patients. In the lixisenatide group, fewer participants experienced symptomatic hypoglycemia (2.5 vs. 7.9%; P<0.05), with fewer gastrointestinal events (especially nausea; 24.5 vs. 35.1%; P<0.05).
Add-on lixisenatide once daily in type 2 diabetes inadequately controlled with metformin demonstrated noninferior improvements in HbA1c, with slightly lower mean weight loss, lower incidence of hypoglycemia, and better gastrointestinal tolerability compared with exenatide twice daily.
比较每日一次利西那肽与每日两次艾塞那肽治疗二甲双胍控制不佳的 2 型糖尿病的疗效和安全性。
在这项 24 周（主要阶段）、开放标签、平行组、多中心研究中，将二甲双胍控制不佳（HbA1c7-10%）的糖尿病成人患者随机分配至每日一次利西那肽 20μg（n=318）或每日两次艾塞那肽 10μg（n=316）组。主要目的是评估利西那肽与艾塞那肽相比在 24 周时 HbA1c 从基线变化的非劣效性。
每日一次利西那肽在 HbA1c 降低方面显示出与每日两次艾塞那肽的非劣效性。利西那肽的最小二乘均值变化为-0.79%（平均降低 7.97 至 7.17%），艾塞那肽为-0.96%（平均降低 7.96 至 7.01%），治疗差异为 0.17%（95%CI，0.033-0.297），符合预先设定的非劣效性上限 CI 边界 0.4%。应答率（HbA1c<7.0%）和空腹血糖改善相当。两种药物均引起体重减轻（利西那肽和艾塞那肽分别从 94.5 降至 91.7kg 和从 96.7 降至 92.9kg）。利西那肽和艾塞那肽的不良事件（AE）发生率相似，严重 AE 的发生率也相似（分别为 2.8%和 2.2%）。因 AE 而停药的患者分别有 33 例（10.4%）和 41 例（13.0%）利西那肽和艾塞那肽。利西那肽组中，症状性低血糖的发生率较低（2.5% vs. 7.9%；P<0.05），胃肠道事件（尤其是恶心）的发生率较低（24.5% vs. 35.1%；P<0.05）。
在二甲双胍控制不佳的 2 型糖尿病患者中，加用每日一次利西那肽治疗可改善 HbA1c，与每日两次艾塞那肽相比，平均体重减轻较少，低血糖发生率较低，胃肠道耐受性更好。
