Yang Wenying, Ji Linong, Zhou Zhiguang, Cain Valerie A, Johnsson Kristina M, Sjöström C David
China-Japan Friendship Hospital, Beijing, China.
Peking University People's Hospital, Beijing, China.
J Diabetes. 2017 Aug;9(8):787-799. doi: 10.1111/1753-0407.12484. Epub 2016 Nov 14.
The efficacy and safety of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, has been demonstrated predominantly in Western populations. This study examined the efficacy and safety of dapagliflozin in Asian patients with type 2 diabetes mellitus (T2DM) from eight Phase IIb/III double-blind trials of up to 24 weeks, treated with placebo (n = 497) or dapagliflozin 5 mg (n = 491) or 10 mg (n = 465).
Efficacy was assessed in the pooled population receiving dapagliflozin 5, 10 mg or placebo over 24 weeks. Safety and tolerability were assessed by collating data for overall adverse events (AEs) and AEs of special interest over the 24-week period.
Demographic and baseline characteristics were comparable across treatment groups. Placebo-corrected adjusted mean changes from baseline at 24 weeks in the dapagliflozin 5 and 10 mg groups, respectively, were -0.52% and -0.58% for HbA1c and -1.34 and -1.80 kg for body weight. Modest reductions in blood pressure were also noted with dapagliflozin. Overall, 56.5%, 53.6%, and 58.7% of patients in the placebo and dapagliflozin 5 and 10 mg groups, respectively, experienced AEs, compared with 2.8%, 4.1%, and 2.4% experiencing serious AEs. Genital infections were more frequent with dapagliflozin 10 mg than placebo, whereas the pattern for urinary tract infections was less clear. A transient reduction in mean estimated glomerular filtration rate was noted with dapagliflozin, but was not associated with an increased frequency of serious renal AEs. In contrast, placebo-corrected reductions in urinary albumin : creatinine ratio in patients with albuminuria at baseline suggest a potential renoprotective effect of dapagliflozin.
Dapagliflozin was efficacious and well tolerated in Asian patients with T2DM.
钠-葡萄糖协同转运蛋白2抑制剂达格列净的疗效和安全性主要在西方人群中得到证实。本研究通过8项长达24周的IIb/III期双盲试验，对亚洲2型糖尿病（T2DM）患者使用达格列净的疗效和安全性进行了研究，这些患者分别接受安慰剂（n = 497）、5 mg达格列净（n = 491）或10 mg达格列净（n = 465）治疗。
对接受5 mg、10 mg达格列净或安慰剂治疗24周的合并人群进行疗效评估。通过整理24周期间总体不良事件（AE）和特殊关注不良事件的数据来评估安全性和耐受性。
各治疗组的人口统计学和基线特征具有可比性。达格列净5 mg组和10 mg组在24周时相对于基线的安慰剂校正调整后平均变化，糖化血红蛋白分别为-0.52%和-0.58%，体重分别为-1.34 kg和-1.80 kg。达格列净还使血压有适度降低。总体而言，安慰剂组、达格列净5 mg组和10 mg组分别有56.5%、53.6%和58.7%的患者发生不良事件，而发生严重不良事件的比例分别为2.8%、4.1%和2.4%。10 mg达格列净组的生殖器感染比安慰剂组更频繁，而尿路感染的情况不太明确。达格列净使平均估计肾小球滤过率出现短暂下降，但与严重肾脏不良事件的发生率增加无关。相比之下，基线时有蛋白尿的患者经安慰剂校正后尿白蛋白：肌酐比值降低，提示达格列净可能具有肾脏保护作用。
达格列净在亚洲T2DM患者中疗效显著且耐受性良好。
