Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial
Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial
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DOI：
10.1016/s0140-6736(13)60683-2
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发表时间：
2013-09-14
期刊：
影响因子：
168.9
通讯作者：
Meininger, Gary
中科院分区：
文献类型：
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作者：
Cefalu, William T.;Leiter, Lawrence A.;Meininger, Gary
背景：钠-葡萄糖共转运体2(SGLT2)抑制剂通过增加尿糖排泄来改善2型糖尿病患者的血糖。我们比较了SGLT2抑制剂Canagliflzin和格列美脲对二甲双胍控制不佳的2型糖尿病患者的疗效和安全性。方法我们于2009年8月28日至2011年12月21日在19个国家的157个中心进行了这项为期52周的随机、双盲、主动对照、3期非劣势试验。将年龄18~80岁、糖化血红蛋白A(1c)(HbA(1c))为7.0%~9.5%、服用稳定二甲双胍的2型糖尿病患者随机分为2组(1：1：1)，分别口服卡那利嗪100 mg、300 mg或格列美脲(上滴度至6 mg、8 mg/d)。患者、研究调查人员和当地赞助人员被蒙面接受治疗。主要终点是糖化血红蛋白(1c)从基线到52周的变化，与格列美脲比较，每个卡那格列齐剂量的非劣势边际为0.3%。如果表现出非劣势，我们根据卡那格列星剂量与格列美脲之间差异的95%可信区间的上限来评估优越性。分析是在改良的意向治疗人群中进行的，包括所有接受至少一剂研究药物的随机患者。这项研究在ClinicalTrials.gov注册，编号NCT00968812。在1452名随机分组的患者中，有1450人接受了至少一剂格列美脲(n=482)、卡那格列齐100 mg(n=483)或卡那格列齐300 mg(n=485)的治疗。52周时降低HBA(1c)时，卡那格列齐100 mg不逊于格列美脲(最小二乘均方差-0.01%[95%CI-0.11至0.09])，卡那格列齐300 mg优于格列美脲(-0.12%[-0.22至-0.02])。格列美脲组有39名患者(8%)发生严重不良事件，而卡那格列酮100毫克组有24名患者(5%)，300毫克组有26名患者(5%)。在100毫克组和300毫克组中，与格列美脲组相比，我们记录到了更多的生殖器真菌感染(女性：26[11%]和34[14%]对5[2%]；男性：17[7%]和20[8%]对3[1%])，尿路感染(31[6%]对22[5%])，以及与渗透性利尿相关的事件(波拉基尿症：两种剂量：12[3%]对1[
Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve glycaemia in patients with type 2 diabetes by enhancing urinary glucose excretion. We compared the efficacy and safety of canagliflozin, an SGLT2 inhibitor, with glimepiride in patients with type 2 diabetes inadequately controlled with metformin.Methods We undertook this 52 week, randomised, double-blind, active-controlled, phase 3 non-inferiority trial at 157 centres in 19 countries between Aug 28, 2009, and Dec 21, 2011. Patients aged 18-80 years with type 2 diabetes and glycated haemoglobin A(1c) (HbA(1c)) of 7.0-9.5% on stable metformin were randomly assigned (1:1:1) by computer-generated random sequence via an interactive voice or web response system to receive canagliflozin 100 mg or 300 mg, or glimepiride (up-titrated to 6 mg or 8 mg per day) orally once daily. Patients, study investigators, and local sponsor personnel were masked to treatment. The primary endpoint was change in HbA(1c) from baseline to week 52, with a non-inferiority margin of 0.3% for the comparison of each canagliflozin dose with glimepiride. If non-inferiority was shown, we assessed superiority on the basis of an upper bound of the 95% CI for the difference of each canagliflozin dose versus glimepiride of less than 0.0%. Analysis was done in a modified intention-to-treat population, including all randomised patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00968812.Findings 1450 of 1452 randomised patients received at least one dose of glimepiride (n=482), canagliflozin 100 mg (n=483), or canagliflozin 300 mg (n=485). For lowering of HbA(1c) at 52 weeks, canagliflozin 100 mg was non-inferior to glimepiride (least-squares mean difference -0.01% [95% CI -0.11 to 0.09]), and canagliflozin 300 mg was superior to glimepiride (-0.12% [-0.22 to -0.02]). 39 (8%) patients had serious adverse events in the glimepiride group versus 24 (5%) in the canagliflozin 100 mg group and 26 (5%) in the 300 mg group. In the canagliflozin 100 mg and 300 mg groups versus the glimepiride group, we recorded a greater number of genital mycotic infections (women: 26 [11%] and 34 [14%] vs five [2%]; men: 17 [7%] and 20 [8%] vs three [1%]), urinary tract infections (31 [6%] for both canagliflozin doses vs 22 [5%]), and osmotic diuresis-related events (pollakiuria: 12 [3%] for both doses vs one [