Efficacy and safety of fasiglifam (TAK-875), a G protein-coupled receptor 40 agonist, in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise: a randomized, double-blind, placebo-controlled, phase III trial.
Efficacy and safety of fasiglifam (TAK-875), a G protein-coupled receptor 40 agonist, in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise: a randomized, double-blind, placebo-controlled, phase III trial.
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DOI：
10.1111/dom.12467
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Matsuno R
中科院分区：
文献类型：
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作者：
Kaku K;Enya K;Nakaya R;Ohira T;Matsuno R
在饮食和运动控制不佳的日本2型糖尿病患者中评估法昔利帆25 mg和50 mg的疗效和安全性。这项III期、双盲、安慰剂对照、多中心研究纳入了192名患者，随机接受每日一次法昔利芬25 mg（n = 63）或50 mg（n = 62）或安慰剂（n = 67）治疗24周。主要疗效终点为第24周糖化血红蛋白（HbA 1c）较基线的变化。在第24周，与安慰剂组相比，两个法昔利芬组的HbA 1c水平均显著降低（p < 0.0001）。安慰剂组HbA 1c较基线的最小二乘平均变化为0.16%，法昔利芬25 mg组为−0.57%，法昔利芬50 mg组为−0.83%。在第24周达到HbA 1c <6.9%目标的患者百分比也显著高于（p < 0.05）法昔利芬25 mg（30.2%）和50 mg（54.8%）安慰剂（13.8%）。从第2周开始，法西立凡在所有评估点均显著降低空腹血糖水平。各法昔利芬组治疗后出现的不良事件的发生率和类型与安慰剂组相似，1例接受法昔利芬50 mg治疗的患者报告了低血糖。任何治疗组的体重均未出现具有临床意义的变化。法昔利芬显著改善了血糖控制，耐受性良好，在饮食和运动控制不佳的日本2型糖尿病患者中低血糖风险较低;然而，在最近对法昔利芬全球临床试验数据的审查中，出现了对肝脏安全性的担忧，并在该试验完成后终止了法昔利芬的临床开发。
To assess the efficacy and safety of fasiglifam 25 and 50 mg in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise. This phase III, double-blind, placebo-controlled, multicentre study included 192 patients randomized to once-daily treatment with fasiglifam 25 mg (n = 63) or 50 mg (n = 62) or placebo (n = 67) for 24 weeks. The primary efficacy endpoint was the change from baseline in glycated haemoglobin (HbA1c) at week 24. At week 24, both fasiglifam groups had significantly reduced HbA1c levels compared with the placebo group (p < 0.0001). The least squares mean change from baseline in HbA1c was 0.16% with placebo, −0.57% with fasiglifam 25 mg and −0.83% with fasiglifam 50 mg. The percentage of patients who achieved an HbA1c target of <6.9% at week 24 was also significantly higher (p < 0.05) for fasiglifam 25 mg (30.2%) and 50 mg (54.8%) compared with placebo (13.8%). Fasiglifam significantly reduced fasting plasma glucose levels at all assessment points, starting from week 2. The incidence and types of treatment-emergent adverse events in each fasiglifam group were similar to those in the placebo group, and hypoglycaemia was reported in 1 patient receiving fasiglifam 50 mg. There were no clinically meaningful changes in body weight in any treatment group. Fasiglifam significantly improved glycaemic control and was well tolerated, with a low risk of hypoglycaemia in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise; however, in a recent review of data from overall fasiglifam global clinical trials, concerns about liver safety arose and the clinical development of fasiglifam was terminated after this trial was completed.