Efficacy and safety of monotherapy with the novel sodium/glucose cotransporter-2 inhibitor tofogliflozin in Japanese patients with type 2 diabetes mellitus: a combined Phase 2 and 3 randomized, placebo-controlled, double-blind, parallel-group comparative study
Efficacy and safety of monotherapy with the novel sodium/glucose cotransporter-2 inhibitor tofogliflozin in Japanese patients with type 2 diabetes mellitus: a combined Phase 2 and 3 randomized, placebo-controlled, double-blind, parallel-group comparative study
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DOI：
10.1186/1475-2840-13-65
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发表时间：
2014-03-28
影响因子：
9.3
通讯作者：
Watanabe, Daisuke
中科院分区：
文献类型：
--
作者：
Kaku, Kohei;Watada, Hirotaka;Watanabe, Daisuke
背景资料：近年来，几种具有新作用机制的口服降糖药物已经上市，扩大了治疗选择的数量。钠/葡萄糖协同转运蛋白-2（SGLT-2）抑制剂是一类新型口服降糖药物，其促进尿糖排泄的机制不依赖于胰岛素。我们报告了一项2期和3期临床研究的结果（Japic CTI-101349）的SGLT 2抑制剂托福格列净（CSG 452，RG 7201）在日本2型糖尿病患者中的应用。在这项多中心、安慰剂对照、随机、一项双盲平行组研究，涉及230例饮食/运动治疗血糖控制不佳的2型糖尿病患者。2010年10月30日至2012年2月28日期间，33个中心的患者随机接受安慰剂（n = 56）或托福格列净（10、20或40 mg;各n = 58）口服治疗，每日一次，持续24周。主要疗效终点为第24周HbA（1c）较基线的变化。结果：总体而言，229例患者被纳入全分析集（安慰剂组：n = 56;托福格列净10 mg组：n = 57;托福格列净20和40 mg组：各n = 58）。最小二乘（LS）均值变化第24周HbA 1c较基线的95%置信区间为-0.028%（-0.192至0.137），而安慰剂组为-0.797%托福格列净10 mg组（-0.960至-0.634），-1.017%（-1.178至-0.856）在托福格列净20 mg组，托福格列净40 mg组为-0.870%（-1.031至-0.709）（所有托福格列净组与安慰剂组的LS均值差异p < 0.0001）。与安慰剂组相比，所有托福格列净组的空腹血糖、餐后2小时血糖和体重均显著降低。主要不良事件为高酮血症、酮尿和尿频。低血糖的发生率较低。此外，大多数不良事件被归类为轻度或中度的severity.Conclusions：Tofoglivaline 10，20，或40毫克，每日一次单药治疗显着降低HbA（1C）和体重，一般耐受性良好，在日本2型糖尿病患者。最近完成了III期研究，并支持这项合并的II期和III期研究的结果。
Background: In recent years, several oral antidiabetic drugs with new mechanisms of action have become available, expanding the number of treatment options. Sodium/glucose cotransporter-2 (SGLT2) inhibitors are a new class of oral antidiabetic drugs with an insulin-independent mechanism promoting urinary glucose excretion. We report the results of a combined Phase 2 and 3 clinical study (Japic CTI-101349) of the SGLT2 inhibitor tofogliflozin (CSG452, RG7201) in Japanese patients with type 2 diabetes mellitus.Methods: The efficacy and safety of tofogliflozin were assessed in this multicenter, placebo-controlled, randomized, double-blind parallel-group study involving 230 patients with type 2 diabetes mellitus with inadequate glycemic control on diet/exercise therapy. Between 30 October 2010 and 28 February 2012, patients at 33 centers were randomized to either placebo (n = 56) or tofogliflozin (10, 20, or 40 mg; n = 58 each) orally, once daily for 24 weeks. The primary efficacy endpoint was the change from baseline in HbA(1c) at week 24.Results: Overall, 229 patients were included in the full analysis set (placebo: n = 56; tofogliflozin 10 mg: n = 57; tofogliflozin 20 and 40 mg: n = 58 each). The least squares (LS) mean change (95% confidence interval) from baseline in HbA1c at week 24 was -0.028% (-0.192 to 0.137) in the placebo group, compared with -0.797% (-0.960 to -0.634) in the tofogliflozin 10 mg group, -1.017% (-1.178 to -0.856) in the tofogliflozin 20 mg group, and -0.870% (-1.031 to -0.709) in the tofogliflozin 40 mg group (p < 0.0001 for the LS mean differences in all tofogliflozin groups vs placebo). There were also prominent decreases in fasting blood glucose, 2-h postprandial glucose, and body weight in all tofogliflozin groups compared with the placebo group. The main adverse events were hyperketonemia, ketonuria, and pollakiuria. The incidence of hypoglycemia was low. Furthermore, most adverse events were classified as mild or moderate in severity.Conclusions: Tofogliflozin 10, 20, or 40 mg administered once daily as monotherapy significantly decreased HbA(1c) and body weight, and was generally well tolerated in Japanese patients with type 2 diabetes mellitus. Phase 3 studies were recently completed and support the findings of this combined Phase 2 and 3 study.