Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial.
Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial.
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DOI：
10.1111/j.1464-5491.2010.03020.x
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发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
DRI6012 Study Investigators
中科院分区：
文献类型：
--
作者：
Ratner RE;Rosenstock J;Boka G;DRI6012 Study Investigators
评价利司那肽（AVE 0010）（一种胰高血糖素样肽-1（GLP-1）受体激动剂）在二甲双胍治疗的2型糖尿病患者中的剂量-反应关系。一项在542例血糖控制不佳[糖化血红蛋白（HbA 1c）≥ 7.0且< 9.0%]的2型糖尿病患者中开展的随机、双盲、安慰剂对照、平行组、13周研究（≥ 53且< 75 mmol/mol）]接受二甲双胍（≥ 1000 mg/天）接受5、10、20或30 μg利司那肽皮下给药，每日一次或每日两次或安慰剂治疗。主要终点是意向治疗人群中HbA 1c从基线至第13周的变化。与基线7.55%相比，利多卡因显著改善了平均HbA 1c（59.0 mmol/mol）; 5、10、20和30 μg剂量的平均降低分别为0.47、0.50、0.69和0.76%（5.1、5.5、7.5和8.3 mmol/mol），每日一次给药，每日两次给药为0.65、0.78、0.75和0.87%（7.1、8.5、8.2和9.5 mmol/mol），安慰剂为0.18%（2.0 mmol/mol）（与安慰剂相比，所有P< 0.01）。68%接受20和30 μg每日一次利司那肽治疗的患者在研究结束时达到目标HbA 1c < 7.0%（53 mmol/mol），32%接受安慰剂治疗（P< 0.0001）。观察到空腹、餐后和平均自我监测七点血糖水平的剂量依赖性改善。利司那肽组的体重变化范围为−2.0至−3.9 kg，安慰剂组为−1.9 kg。最常见的不良事件是轻度至中度恶心。在接受二甲双胍治疗的2型糖尿病轻度高血糖患者中，利多卡因可显著改善血糖控制。观察到每日一次和每日两次方案的剂量-效应关系，疗效水平相似，20 μg每日一次剂量的利司那肽证明了最佳疗效-耐受性比。这种新的，每日一次的GLP-1受体激动剂在2型糖尿病的管理中显示出希望，将通过正在进行的长期研究进一步确定。
To evaluate the dose–response relationship of lixisenatide (AVE0010), a glucagon-like peptide-1 (GLP-1) receptor agonist, in metformin-treated patients with Type 2 diabetes. Randomized, double-blind, placebo-controlled, parallel-group, 13 week study of 542 patients with Type 2 diabetes inadequately controlled [glycated haemoglobin (HbA1c) ≥ 7.0 and < 9.0% (≥ 53 and < 75 mmol/mol)] on metformin (≥ 1000 mg/day) treated with subcutaneous lixisenatide doses of 5, 10, 20 or 30 μg once daily or twice daily or placebo. The primary end-point was change in HbA1c from baseline to 13 weeks in the intent-to-treat population. Lixisenatide significantly improved mean HbA1c from a baseline of 7.55% (59.0 mmol/mol); respective mean reductions for 5, 10, 20 and 30 μg doses were 0.47, 0.50, 0.69 and 0.76% (5.1, 5.5, 7.5 and 8.3 mmol/mol), on once-daily and 0.65, 0.78, 0.75 and 0.87% (7.1, 8.5, 8.2 and 9.5 mmol/mol) on twice-daily administrations vs. 0.18% (2.0 mmol/mol) with placebo (all P< 0.01 vs. placebo). Target HbA1c < 7.0% (53 mmol/mol) at study end was achieved in 68% of patients receiving 20 and 30 μg once-daily lixisenatide vs. 32% receiving placebo (P< 0.0001). Dose-dependent improvements were observed for fasting, postprandial and average self-monitored seven-point blood glucose levels. Weight changes ranged from −2.0 to −3.9 kg with lixisenatide vs. −1.9 kg with placebo. The most frequent adverse event was mild-to-moderate nausea. Lixisenatide significantly improved glycaemic control in mildly hyperglycaemic patients with Type 2 diabetes on metformin. Dose–response relationships were seen for once- and twice-daily regimens, with similar efficacy levels, with a 20 μg once-daily dose of lixisenatide demonstrating the best efficacy-to-tolerability ratio. This new, once-daily GLP-1 receptor agonist shows promise in the management of Type 2 diabetes to be defined further by ongoing long-term studies.
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影响因子：
2.2
作者：
Tews, D.;Werner, U.;Eckel, J.
通讯作者：
Eckel, J.
影响因子：
158.5
作者：
Gerstein, Hertzel C.;Miller, Michael E.;Friedewald, William T.
通讯作者：
Friedewald, William T.
影响因子：
16.2
作者：
Kendall, DM;Riddle, MC;Baron, AD
通讯作者：
Baron, AD
影响因子：
5.8
作者：
Nauck, MA;Heimesaat, MM;Schmiegel, WH
通讯作者：
Schmiegel, WH
DOI：
10.1124/jpet.103.051987
发表时间：
2003-11-01
影响因子：
3.5
作者：
Thorkildsen, C;Neve, S;Petersen, JS
通讯作者：
Petersen, JS