Efficacy and safety of twice-daily treatment with canagliflozin, a sodium glucose co-transporter 2 inhibitor, added on to metformin monotherapy in patients with type 2 diabetes mellitus.
Efficacy and safety of twice-daily treatment with canagliflozin, a sodium glucose co-transporter 2 inhibitor, added on to metformin monotherapy in patients with type 2 diabetes mellitus.
复制标题
DOI：
10.1016/j.jcte.2014.04.001
复制
发表时间：
2014-06
影响因子：
3
通讯作者：
Meininger G
中科院分区：
文献类型：
--
作者：
Qiu R;Capuano G;Meininger G
目的：评价卡那格列津每日两次(BID)与安慰剂治疗2型糖尿病(T2 DM)患者二甲双胍的疗效和安全性。在这项为期18周的随机、双盲、安慰剂对照研究中，7个国家和地区的60个中心的患者(N=279)接受了50或150 mg的Canagliflzin或安慰剂Bid。预先指定的主要终点是在第18周时HbA1c较基线的变化。预先指定的次要终点包括达到HbA1c和7.0%的患者比例、空腹血糖(FPG)变化和体重变化百分比；还评估了收缩压(BP)和空腹血脂的变化。在整个研究过程中记录不良事件(AEs)。在第18周，从平均基线HbA1c 7.6%(60 mg/摩尔)开始，与安慰剂相比，Canagliflzin 50和150mgBid显著降低HbA1c(−分别为0.45%，−0.61%，−0.01%[−5，−7，−0.1mmoL/mo1]；P<；0.001)。与安慰剂相比，接受卡那格列齐治疗的患者糖化血红蛋白达到7.0%的患者更多(P<0.05)。与安慰剂相比，两种剂量的Canagliflzin都显著降低了空腹血糖和体重(P<0.001)，并降低了收缩压。使用50和150 mg卡那格列齐，Bid和安慰剂的总体AE发生率分别为35.5%，40.9%和36.6%。Canagliflzin与尿路感染、女性生殖器真菌感染和渗透性利尿相关的不良反应的发生率增加有关；这些导致的停药很少。记录在案的低血糖发生率跨组很低。Canagliflzin 50和150 mg Bid提供了显著的血糖疗效和体重减轻，在服用背景二甲双胍的T2 DM患者中总体耐受性良好。临床试验.gov识别符：NCT01340664 Canagliflzin Bid在服用二甲双胍的2型糖尿病患者中进行评估。与安慰剂相比，卡那格列齐50和150毫克BID显著降低HbA1c。这两种剂量还可以降低空腹血糖、体重和血压。疗效研究结果与卡那格列齐100 mg和300 mg每日一次的研究一致。卡那格列星BID的耐受性一般良好，与卡那格列星qd相似。
To evaluate the efficacy/safety of canagliflozin twice daily (BID) compared with placebo in patients with type 2 diabetes mellitus (T2DM) on metformin. In this 18-week, randomized, double-blind, placebo-controlled study, patients (N = 279) at 60 centers in 7 countries received canagliflozin 50 or 150 mg or placebo BID. The pre-specified primary endpoint was change from baseline in HbA1c at Week 18. Pre-specified secondary endpoints included proportion of patients reaching HbA1c <7.0%, change in fasting plasma glucose (FPG), and percent change in body weight; changes in systolic blood pressure (BP) and fasting plasma lipids were also evaluated. Adverse events (AEs) were recorded throughout the study. From a mean baseline HbA1c of 7.6% (60 mmol/mol), canagliflozin 50 and 150 mg BID significantly reduced HbA1c compared with placebo at Week 18 (−0.45%, −0.61%, −0.01% [−5, −7, −0.1 mmol/mol], respectively; P < 0.001). More patients achieved HbA1c <7.0% with canagliflozin than placebo (P < 0.05). Relative to placebo, both canagliflozin doses significantly lowered FPG and body weight (P < 0.001), and reduced systolic BP. Overall AE incidence was 35.5%, 40.9%, and 36.6% with canagliflozin 50 and 150 mg BID and placebo, respectively. Canagliflozin was associated with increased incidences of urinary tract infections, female genital mycotic infections, and osmotic diuresis-related AEs; these led to few discontinuations. The incidence of documented hypoglycemia was low across groups. Canagliflozin 50 and 150 mg BID provided significant glycemic efficacy and body weight reduction, and were generally well tolerated in patients with T2DM on background metformin. ClinicalTrials.gov Identifier: NCT01340664 Canagliflozin BID was evaluated in patients with type 2 diabetes on metformin. Canagliflozin 50 and 150 mg BID significantly reduced HbA1c vs placebo. Both doses also lowered fasting plasma glucose, body weight, and blood pressure. Efficacy findings were consistent with studies of canagliflozin 100 and 300 mg QD. Canagliflozin BID was generally well tolerated, similar to canagliflozin QD.