恩格列净单药治疗对日本2型糖尿病患者餐后血糖及24小时血糖变异性的影响：一项随机、双盲、安慰剂对照的4周研究。
Effect of empagliflozin monotherapy on postprandial glucose and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, 4-week study.
作者信息
Nishimura Rimei, Tanaka Yuko, Koiwai Kazuki, Inoue Kohei, Hach Thomas, Salsali Afshin, Lund Søren S, Broedl Uli C
机构信息
Jikei University School of Medicine, Tokyo, Japan.
Nippon Boehringer Ingelheim Co. Ltd, Osaki 2-1-1, ThinkPark Tower, Tokyo, 141-6017, Japan.
出版信息
Cardiovasc Diabetol. 2015 Jan 30;14:11. doi: 10.1186/s12933-014-0169-9.
BACKGROUND
This study evaluated the effect of empagliflozin on postprandial glucose (PPG) and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus (T2DM).
METHODS
Patients (N = 60; baseline mean [SD] HbA1c 7.91 [0.80]%; body mass index 24.3 [3.2] kg/m(2)) were randomized to receive empagliflozin 10 mg (n = 20), empagliflozin 25 mg (n = 19) or placebo (n = 21) once daily as monotherapy for 28 days. A meal tolerance test and continuous glucose monitoring (CGM) for 24 hours were performed at baseline and on days 1 and 28. The primary endpoint was change from baseline in area under the glucose concentration-time curve 3 hours after breakfast (AUC1-4h for PPG) at day 28.
RESULTS
Adjusted mean (95%) differences versus placebo in changes from baseline in AUC1-4h for PPG at day 1 were -97.1 (-126.5, -67.8) mg · h/dl with empagliflozin 10 mg and -91.6 (-120.4, -62.8) mg · h/dl with empagliflozin 25 mg (both p < 0.001 versus placebo) and at day 28 were -85.5 (-126.0, -45.0) mg · h/dl with empagliflozin 10 mg and -104.9 (-144.8, -65.0) mg · h/dl with empagliflozin 25 mg (both p < 0.001 versus placebo). Adjusted mean (95% CI) differences versus placebo in change from baseline in 24-hour mean glucose (CGM) at day 1 were -20.8 (-27.0, -14.7) mg/dl with empagliflozin 10 mg and -23.9 (-30.0, -17.9) mg/dl with empagliflozin 25 mg (both p < 0.001 versus placebo) and at day 28 were -24.5 (-35.4, -13.6) mg/dl with empagliflozin 10 mg and -31.7 (-42.5,-20.9) mg/dl with empagliflozin 25 mg (both p < 0.001 versus placebo). Changes from baseline in mean amplitude of glucose excursions (MAGE; CGM) were not significantly different with either empagliflozin dose versus placebo at either timepoint. Curves of mean glucose (CGM) did not change between baseline and day 1 or 28 with placebo, but shifted downward with empagliflozin. Percentage of time with glucose ≥70 to <180 mg/dl increased from 52.0% at baseline to 77.0% at day 28 with empagliflozin 10 mg and from 55.0% to 81.1% with empagliflozin 25 mg, without increasing time spent with hypoglycemia.
CONCLUSION
Empagliflozin for 28 days reduced PPG from the first day and improved daily blood glucose control in Japanese patients with T2DM.
TRIAL REGISTRATION
Clinicaltrials.gov NCT01947855.
背景
本研究评估了恩格列净对日本2型糖尿病（T2DM）患者餐后血糖（PPG）及24小时血糖变异性的影响。
方法
患者（N = 60；基线时平均[标准差]糖化血红蛋白A1c为7.91[0.80]%；体重指数为24.3[3.2]kg/m²）被随机分为三组，分别接受每日一次10 mg恩格列净（n = 20）、25 mg恩格列净（n = 19）或安慰剂（n = 21）单药治疗，为期28天。在基线、第1天和第28天进行了进餐耐量试验及24小时持续葡萄糖监测（CGM）。主要终点为第28天早餐后3小时葡萄糖浓度 - 时间曲线下面积（PPG的AUC1 - 4h）相对于基线的变化。
结果
第1天，与安慰剂相比，10 mg恩格列净组PPG的AUC1 - 4h自基线变化的调整后平均（95%）差值为 -97.1（-126.5，-67.8）mg·h/dl，25 mg恩格列净组为 -91.6（-120.4，-62.8）mg·h/dl（两者与安慰剂相比p均<0.001）；第28天，10 mg恩格列净组为 -85.5（-126.0，-45.0）mg·h/dl，25 mg恩格列净组为 -104.9（-144.8，-65.0）mg·h/dl（两者与安慰剂相比p均<0.001）。第1天，与安慰剂相比，10 mg恩格列净组24小时平均血糖（CGM）自基线变化的调整后平均（95%CI）差值为 -20.8（-27.0，-14.7）mg/dl，25 mg恩格列净组为 -23.9（-30.0，-17.9）mg/dl（两者与安慰剂相比p均<0.001）；第28天，10 mg恩格列净组为 -24.5（-35.4，-13.6）mg/dl，25 mg恩格列净组为 -31.7（-42.5，-20.9）mg/dl（两者与安慰剂相比p均<0.001）。在任一观察时间点，与安慰剂相比，两种恩格列净剂量组的葡萄糖波动平均幅度（MAGE；CGM）自基线的变化均无显著差异。安慰剂组平均血糖（CGM）曲线在基线与第1天或第28天之间未发生变化，但恩格列净组曲线向下偏移。使用10 mg恩格列净时，血糖≥70至<180 mg/dl的时间百分比从基线时的52.0%增至第28天的77.0%，使用25 mg恩格列净时则从55.0%增至81.1%，且低血糖时间未增加。
结论
恩格列净治疗28天可从第一天起降低PPG，并改善日本T2DM患者的每日血糖控制。
试验注册
Clinicaltrials.gov NCT01947855
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