Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with type 2 diabetes.
Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with type 2 diabetes.
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DOI：
10.2337/dc11-1926
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发表时间：
2012-06
期刊：
影响因子：
16.2
通讯作者：
Canagliflozin DIA 2001 Study Group
中科院分区：
文献类型：
--
作者：
Rosenstock J;Aggarwal N;Polidori D;Zhao Y;Arbit D;Usiskin K;Capuano G;Canovatchel W;Canagliflozin DIA 2001 Study Group
旨在评估卡格列净（一种钠-葡萄糖协同转运蛋白 2 抑制剂）对二甲双胍单药治疗未能充分控制的 2 型糖尿病的疗效。这是一项双盲、安慰剂对照、平行组、多中心、剂量范围研究，451 名受试者随机接受卡格列净 50、100、200 或 300 mg 每日一次 (QD) 或 300 mg 每日两次 (BID)、西他列汀 100 mg QD 或安慰剂。主要终点是从基线到第 12 周的 A1C 变化。次要终点包括空腹血糖 (FPG)、体重和隔夜尿糖与肌酐比值的变化。还评估了安全性和耐受性。从基线（7.6-8.0%）到第12周，卡格列净与A1C显着降低相关：卡格列净50、100、200、300 mg QD和300 mg BID分别为-0.79、-0.76、-0.70、-0.92和-0.95%，而安慰剂为-0.22%（所有P < 0.001)，西格列汀为-0.74%。 FPG 降低了-16 至-27 mg/dL，体重降低了-2.3% 至-3.4%，尿糖与肌酐比值显着增加。不良事件是短暂的、轻度至中度的，并且在各组中是平衡的，除了卡格列净 (3-8%) 与安慰剂和西他列汀 (2%) 相比，症状性生殖器感染出现非剂量依赖性增加。据报道，卡格列净组、安慰剂组和西他列汀组的尿路感染率分别为 3-9%、6% 和 2%，无剂量依赖性。低血糖的总体发生率较低。卡格列净添加到二甲双胍中可显着改善 2 型糖尿病的血糖控制，并与低血糖发生率低和体重显着减轻相关。除女性生殖器感染频率增加外，卡格列净的安全性/耐受性良好。
To evaluate the effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, in type 2 diabetes mellitus inadequately controlled with metformin monotherapy. This was a double-blind, placebo-controlled, parallel-group, multicenter, dose-ranging study in 451 subjects randomized to canagliflozin 50, 100, 200, or 300 mg once daily (QD) or 300 mg twice daily (BID), sitagliptin 100 mg QD, or placebo. Primary end point was change in A1C from baseline through week 12. Secondary end points included change in fasting plasma glucose (FPG), body weight, and overnight urinary glucose-to-creatinine ratio. Safety and tolerability were also assessed. Canagliflozin was associated with significant reductions in A1C from baseline (7.6–8.0%) to week 12: −0.79, −0.76, −0.70, −0.92, and −0.95% for canagliflozin 50, 100, 200, 300 mg QD and 300 mg BID, respectively, versus −0.22% for placebo (all P < 0.001) and −0.74% for sitagliptin. FPG was reduced by −16 to −27 mg/dL, and body weight was reduced by −2.3 to −3.4%, with significant increases in urinary glucose-to-creatinine ratio. Adverse events were transient, mild to moderate, and balanced across arms except for a non–dose-dependent increase in symptomatic genital infections with canagliflozin (3–8%) versus placebo and sitagliptin (2%). Urinary tract infections were reported without dose dependency in 3–9% of canagliflozin, 6% of placebo, and 2% of sitagliptin arms. Overall incidence of hypoglycemia was low. Canagliflozin added onto metformin significantly improved glycemic control in type 2 diabetes and was associated with low incidence of hypoglycemia and significant weight loss. The safety/tolerability profile of canagliflozin was favorable except for increased frequency of genital infections in females.