Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial.
Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial.
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DOI：
10.1007/s00125-013-3039-1
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发表时间：
2013-12
期刊：
影响因子：
8.2
通讯作者：
Meininger, G.
中科院分区：
文献类型：
--
作者：
Lavalle-Gonzalez, F. J.;Januszewicz, A.;Davidson, J.;Tong, C.;Qiu, R.;Canovatchel, W.;Meininger, G.
关键词：
本研究的目的是评估卡格列净与安慰剂和西格列汀在接受背景二甲双胍治疗的2型糖尿病患者中的疗效和安全性。这项随机、双盲、四组、平行组的三期研究于2010年4月至2012年8月在22个国家的169个中心进行。接受二甲双胍治疗的2型糖尿病患者（N = 1284），年龄≥18岁，≤80岁，血糖控制不充分（HbA1c≥7.0% [53 mmol/mol]和≤10.5% [91 mmol/mol]），接受卡格列净（100 mg或300 mg）、西格列汀（100 mg）或安慰剂（N = 368,367,366,183），为期26周，分别为安慰剂和活性控制期，随后为26周。活动控制期（安慰剂组改用西格列汀[安慰剂/西格列汀]），纳入修改意向治疗分析集。随机化使用计算机生成的时间表进行；参与者、研究中心和赞助商对小组分配不知情。主要终点是第26周时HbA1c较基线的变化；次要终点包括HbA1c（第52周）、空腹血糖（FPG）、体重和收缩压（BP，第26周和第52周）的变化。在整个研究过程中记录不良事件（ae）。在第26周，与安慰剂相比，canagliflozin 100 mg和300 mg降低了HbA1c（分别为- 0.79%,-0.94%,-0.17%;p < 0.001）。在第52周，与西格列汀相比，卡格列净100 mg和300 mg在降低HbA1c方面表现出非劣效性，卡格列净300 mg在降低HbA1c方面表现出统计学优势（分别为-0.73%、-0.88%和-0.73%）；与西格列汀的差异（95% CI）分别为0%（- 0.12,0.12）和- 0.15%（- 0.27,-0.03）。与安慰剂（第26周：-3.7%,-4.2%,-1.2%;p < 0.001）和西格列汀（第52周：-3.8%,-4.2%,-1.3%;p < 0.001）相比，100 mg和300 mg的Canagliflozin降低了体重。与安慰剂（第26周）和西格列汀（第52周）相比，canaglilozin剂量降低了FPG和收缩压（p < 0.001）。总的AE和AE相关的停药率在各组之间大致相似，但卡格列净100mg组的停药率更高。卡格列净组生殖器真菌感染和渗透利尿素相关AE发生率较高；很少导致停产。卡格列净组低血糖发生率较高。与安慰剂（第26周）和西格列汀（第52周）相比，Canagliflozin改善了血糖并降低了体重，并且在使用二甲双胍的2型糖尿病患者中通常具有良好的耐受性。这项研究得到了Janssen Research & Development， LLC的支持。本文的在线版本（doi:10.1007/s00125-013-3039-1）包含同行评审但未经编辑的补充材料，授权用户可获得。
The aim of this work was to evaluate the efficacy and safety of canagliflozin vs placebo and sitagliptin in patients with type 2 diabetes who were being treated with background metformin. This randomised, double-blind, four-arm, parallel-group, Phase 3 study was conducted at 169 centres in 22 countries between April 2010 and August 2012. Participants (N = 1,284) with type 2 diabetes aged ≥18 and ≤80 years who had inadequate glycaemic control (HbA1c ≥7.0% [53 mmol/mol] and ≤10.5% [91 mmol/mol]) on metformin therapy received canagliflozin 100 mg or 300 mg, sitagliptin 100 mg, or placebo (n = 368, 367, 366, 183, respectively) for a 26 week, placebo- and active-controlled period followed by a 26 week, active-controlled period (placebo group switched to sitagliptin [placebo/sitagliptin]) and were included in the modified intent-to-treat analysis set. Randomisation was performed using a computer-generated schedule; participants, study centres and the sponsor were blinded to group assignment. The primary endpoint was change from baseline in HbA1c at week 26; secondary endpoints included changes in HbA1c (week 52) and fasting plasma glucose (FPG), body weight, and systolic blood pressure (BP; weeks 26 and 52). Adverse events (AEs) were recorded throughout the study. At week 26, canagliflozin 100 mg and 300 mg reduced HbA1c vs placebo (−0.79%, –0.94%, –0.17%, respectively; p < 0.001). At week 52, canagliflozin 100 mg and 300 mg demonstrated non-inferiority, and canagliflozin 300 mg demonstrated statistical superiority, to sitagliptin in lowering HbA1c (−0.73%, –0.88%,–0.73%, respectively); differences (95% CI) vs sitagliptin were 0% (−0.12, 0.12) and −0.15% (−0.27, –0.03), respectively. Canagliflozin 100 mg and 300 mg reduced body weight vs placebo (week 26: –3.7%, –4.2%, –1.2%, respectively; p < 0.001) and sitagliptin (week 52: –3.8%, –4.2%, –1.3%, respectively; p < 0.001). Both canagliflozin doses reduced FPG and systolic BP vs placebo (week 26) and sitagliptin (week 52) (p < 0.001). Overall AE and AE-related discontinuation rates were generally similar across groups, but higher with canagliflozin 100 mg. Genital mycotic infection and osmotic diuresis-related AE rates were higher with canagliflozin; few led to discontinuations. Hypoglycaemia incidence was higher with canagliflozin. Canagliflozin improved glycaemia and reduced body weight vs placebo (week 26) and sitagliptin (week 52) and was generally well tolerated in patients with type 2 diabetes on metformin. ClinicalTrials.gov NCT01106677 This study was supported by Janssen Research & Development, LLC. The online version of this article (doi:10.1007/s00125-013-3039-1) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
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影响因子：
5.8
作者：
Ferrannini, E.;Seman, L.;Woerle, H. J.
通讯作者：
Woerle, H. J.
影响因子：
168.9
作者：
Bailey, Clifford J.;Gross, Jorge L.;List, James F.
通讯作者：
List, James F.
DOI：
10.1111/dom.12090
发表时间：
2013-05
期刊：
Diabetes, obesity & metabolism
影响因子：
--
作者：
Yale JF;Bakris G;Cariou B;Yue D;David-Neto E;Xi L;Figueroa K;Wajs E;Usiskin K;Meininger G
通讯作者：
Meininger G
达帕格列非佐以二甲双胍治疗二甲双胍控制不佳的 2 型糖尿病：一项为期 102 周的随机、双盲、安慰剂对照试验。
影响因子：
9.3
作者：
Bailey CJ;Gross JL;Hennicken D;Iqbal N;Mansfield TA;List JF
通讯作者：
List JF
影响因子：
16.2
作者：
Rosenstock J;Aggarwal N;Polidori D;Zhao Y;Arbit D;Usiskin K;Capuano G;Canovatchel W;Canagliflozin DIA 2001 Study Group
通讯作者：
Canagliflozin DIA 2001 Study Group