China-Japan Friendship Hospital, Beijing, China.
Eulji General Hospital, Seoul, South Korea.
Diabetes Obes Metab. 2018 Feb;20(2):335-343. doi: 10.1111/dom.13072. Epub 2017 Oct 5.
To assess the effects on glycaemic control of lixisenatide vs placebo as add-on treatment to basal insulin (BI) ± metformin and effects on glycated haemoglobin (HbA1c) reduction in patients with insufficiently controlled type 2 diabetes (T2D).
Patients (n = 448) with inadequately controlled T2D were randomized (1:1) to lixisenatide or placebo as add-on to BI ± metformin for 24 weeks after an 8-week run-in phase, during which BI was titrated to a target self-monitored plasma glucose (SMPG; 4.4-5.6 mmol/L). The primary endpoint was absolute change in HbA1c from baseline to week 24. Secondary efficacy endpoints included: percentage of responders; changes in 2-hour postprandial plasma glucose (PPG); 7-point SMPG (daily average); body weight (BW); total daily BI dose; fasting plasma glucose; and safety assessments.
Baseline demographics were similar in the two treatment groups. After insulin optimization during run-in, lixisenatide was superior to placebo in mean change from baseline (7.9% [standard deviation {s.d.}, 0.66] and 7.9% [0.70], respectively) to week 24 in HbA1c (least squares mean [standard error {s.e.}] change -0.62% [0.09] vs -0.11% [0.09]; P < .0001, respectively) and higher proportions of patients achieved HbA1c targets. Two-hour PPG, daily mean SMPG and mean BW were reduced further and daily BI dose was lower with lixisenatide than placebo (-1.12 kg vs 0.04 kg [P < .0001]; -3.0 U vs -1.9 U [P = .0033], respectively). Treatment-emergent adverse events were greater with lixisenatide than placebo (63.8% vs 40.8%, respectively). The incidence of symptomatic hypoglycaemia was similar (lixisenatide 15.6% vs placebo 13.5%).
In Asian patients insufficiently controlled on BI ± metformin, lixisenatide was superior to placebo in glycaemic control, with a tolerability profile in line with other glucagon-like peptide-1 receptor agonists.
NCT01632163 (clinicaltrials.gov).
评估利西那肽与安慰剂作为基础胰岛素（BI）±二甲双胍的附加治疗在血糖控制方面的作用，以及在血糖控制不佳的 2 型糖尿病（T2D）患者中降低糖化血红蛋白（HbA1c）的作用。
在 8 周的导入期后，将血糖控制不佳的 448 例 T2D 患者随机（1:1）分为利西那肽或安慰剂组，作为 BI±二甲双胍的附加治疗，持续 24 周，在此期间，BI 滴定至自我监测血浆葡萄糖（SMPG；4.4-5.6mmol/L）的目标。主要终点是从基线到第 24 周 HbA1c 的绝对变化。次要疗效终点包括：应答者的百分比；餐后 2 小时血糖（PPG）的变化；7 点 SMPG（每日平均值）；体重（BW）；总日 BI 剂量；空腹血糖；和安全性评估。
两组治疗的基线人口统计学特征相似。在导入期胰岛素优化后，利西那肽在 HbA1c 方面优于安慰剂，从基线（7.9%[标准差{sd}，0.66]和 7.9%[0.70]）到第 24 周的平均变化为-0.62%[0.09] vs -0.11%[0.09]；P<0.0001，分别），更多的患者达到了 HbA1c 目标。与安慰剂相比，利西那肽进一步降低了餐后 2 小时 PPG、每日平均 SMPG 和平均 BW，并且每日 BI 剂量更低（-1.12kg vs 0.04kg[P<0.0001]；-3.0U vs -1.9U[P=0.0033]，分别）。利西那肽的治疗相关不良事件发生率高于安慰剂（分别为 63.8%和 40.8%）。症状性低血糖的发生率相似（利西那肽 15.6%，安慰剂 13.5%）。
在亚洲血糖控制不佳的 BI±二甲双胍患者中，利西那肽在血糖控制方面优于安慰剂，其耐受性与其他胰高血糖素样肽-1 受体激动剂一致。
NCT01632163（clinicaltrials.gov）。
