Canagliflozin improves glycaemic control over 28 days in subjects with type 2 diabetes not optimally controlled on insulin
Canagliflozin improves glycaemic control over 28 days in subjects with type 2 diabetes not optimally controlled on insulin
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DOI：
10.1111/j.1463-1326.2012.01558.x
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发表时间：
2012-06-01
影响因子：
5.8
通讯作者：
Schwartz, S.
中科院分区：
文献类型：
--
作者：
Devineni, D.;Morrow, L.;Schwartz, S.
目的：卡格列净是一种钠-葡萄糖协同转运蛋白2（SGLT 2）抑制剂，正在研究用于治疗2型糖尿病（T2 DM）。研究方法：这是一项在两个研究中心进行的随机化、双盲、安慰剂对照、平行组、28天研究，在29例接受胰岛素和最多一种口服抗高血压药物治疗后血糖控制不佳的T2 DM受试者中进行。受试者接受卡格列净100 mg QD或300 mg每日两次BID或安慰剂治疗。检查了卡格列净的安全性、耐受性、药代动力学特征和药效学作用。还检查了75克口服葡萄糖激发后的葡萄糖吸收不良。结果：卡格列净的药代动力学呈剂量依赖性，消除半衰期范围为12 - 15 h。28天后，接受卡格列净A1 C降低治疗的受试者中，葡萄糖排泄的肾阈值降低;尿糖排泄增加; A1 C、空腹血糖和体重降低：安慰剂组为0.19%，100 mg QD组为0.73%，300 mg BID组为0.92%;体重变化：安慰剂增加0.03 kg，100 mg QD减少0.73 kg，300 mg BID减少1.19 kg）。卡格列净治疗未观察到葡萄糖吸收不良。无死亡、严重不良事件或重度低血糖发作。各组不良事件的发生率相似。常规实验室安全性检查、生命体征或心电图未发生具有临床意义的变化。结论：在接受胰岛素和口服抗高血压治疗的受试者中，卡格列净耐受良好，无葡萄糖吸收不良证据，药代动力学特征与每日一次给药一致，并改善了血糖控制。
Aim: Canagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that is being investigated for the treatment of type 2 diabetes mellitus (T2DM). Methods: This was a randomized, double-blind, placebo-controlled, parallel-group, 28-day study conducted at two sites, in 29 subjects with T2DM not optimally controlled on insulin and up to one oral antihyperglycaemic agent. Subjects were treated with canagliflozin 100 mg QD or 300 mg twice daily BID) or placebo. Safety, tolerability, pharmacokinetic characteristics and pharmacodynamic effects of canagliflozin were examined. Glucose malabsorption following a 75-g oral glucose challenge was also examined. Results: Canagliflozin pharmacokinetics were dose-dependent, and the elimination half-life ranged from 12 to 15 h. After 28 days, the renal threshold for glucose excretion was reduced; urinary glucose excretion was increased; and A1C, fasting plasma glucose and body weight decreased in subjects administered canagliflozin A1C reductions: 0.19% with placebo, 0.73% with 100 mg QD, 0.92% with 300 mg BID; body weight changes: 0.03 kg increase with placebo, 0.73 kg reduction with 100 mg QD, 1.19 kg reduction with 300 mg BID). Glucose malabsorption was not observed with canagliflozin treatment. There were no deaths, serious adverse events or severe hypoglycaemic episodes. The incidence of adverse events was similar across groups. There were no clinically meaningful changes in routine laboratory safety tests, vital signs or electrocardiograms. Conclusion: In subjects receiving insulin and oral antihyperglycaemic therapy, canagliflozin was well tolerated without evidence for glucose malabsorption, had pharmacokinetic characteristics consistent with once-daily dosing, and improved glycaemic control.