Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease.
Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease.
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DOI：
10.1111/dom.12090
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Meininger G
中科院分区：
文献类型：
--
作者：
Yale JF;Bakris G;Cariou B;Yue D;David-Neto E;Xi L;Figueroa K;Wajs E;Usiskin K;Meininger G
卡格列净是一种正在开发的钠葡萄糖协同转运蛋白2抑制剂，用于治疗2型糖尿病（T2 DM）。本研究评价了卡格列净在T2 DM和3期慢性肾病[CKD;估计肾小球滤过率（eGFR）≥30且<50 ml/min/1.73 m2]受试者中的疗效和安全性。在这项随机、双盲、安慰剂对照、III期试验中，受试者（N = 269）每日接受卡格列净100或300 mg或安慰剂。主要疗效终点为第26周时HbA 1c较基线的变化。预先设定的次要终点为空腹血糖（FPG）的变化和达到HbA 1c <7.0%的受试者比例。根据不良事件（AE）报告评估安全性;还评价了肾脏安全性参数（例如eGFR、血尿素氮和白蛋白/肌酐比值）。与安慰剂相比，卡格列净100和300 mg在第26周均降低了HbA 1c（-0.33、-0.44和-0.03%; p < 0.05）。卡格列净100 mg和300 mg组与安慰剂组相比，FPG数值降低和HbA 1c < 7.0%的受试者比例较高（27.3%、32.6%和17.2%）。卡格列净100和300 mg与安慰剂组的总体AE发生率相似（78.9、74.2和74.4%）。与其他组相比，卡格列净300 mg组观察到尿路感染和渗透性利尿相关AE以及血管内容量减少的发生率略高。在卡格列净组中观察到肾功能参数的一过性变化，在26周内趋于基线。卡格列净改善了T2 DM和3期CKD受试者的血糖控制，并且通常耐受良好。
Canagliflozin is a sodium glucose co-transporter 2 inhibitor in development for treatment of type 2 diabetes mellitus (T2DM). This study evaluated the efficacy and safety of canagliflozin in subjects with T2DM and stage 3 chronic kidney disease [CKD; estimated glomerular filtration rate (eGFR) ≥30 and <50 ml/min/1.73 m2]. In this randomized, double-blind, placebo-controlled, phase 3 trial, subjects (N = 269) received canagliflozin 100 or 300 mg or placebo daily. The primary efficacy endpoint was change from baseline in HbA1c at week 26. Prespecified secondary endpoints were change in fasting plasma glucose (FPG) and proportion of subjects reaching HbA1c <7.0%. Safety was assessed based on adverse event (AE) reports; renal safety parameters (e.g. eGFR, blood urea nitrogen and albumin/creatinine ratio) were also evaluated. Both canagliflozin 100 and 300 mg reduced HbA1c from baseline compared with placebo at week 26 (–0.33, –0.44 and –0.03%; p < 0.05). Numerical reductions in FPG and higher proportions of subjects reaching HbA1c < 7.0% were observed with canagliflozin 100 and 300 mg versus placebo (27.3, 32.6 and 17.2%). Overall AE rates were similar for canagliflozin 100 and 300 mg and placebo (78.9, 74.2 and 74.4%). Slightly higher rates of urinary tract infections and AEs related to osmotic diuresis and reduced intravascular volume were observed with canagliflozin 300 mg compared with other groups. Transient changes in renal function parameters that trended towards baseline over 26 weeks were observed with canagliflozin. Canagliflozin improved glycaemic control and was generally well tolerated in subjects with T2DM and Stage 3 CKD.
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影响因子：
168.9
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