Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial
Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial
复制标题
DOI：
10.1016/s0140-6736(10)60407-2
复制
发表时间：
2010-06-01
期刊：
影响因子：
168.9
通讯作者：
List, James F.
中科院分区：
文献类型：
--
作者：
Bailey, Clifford J.;Gross, Jorge L.;List, James F.
背景纠正高血糖和预防葡萄糖毒性是2型糖尿病治疗的重要目标。达格列净是一种选择性钠-葡萄糖协同转运蛋白-2抑制剂，以胰岛素非依赖性方式减少肾脏葡萄糖重吸收。我们评估了达格列净在二甲双胍血糖控制不佳患者中的疗效和安全性。方法在这项3期、多中心、双盲、平行组、安慰剂对照试验中，546例每日接受二甲双胍治疗的2型糖尿病成人患者（>= 1500 mg/天）和血糖控制不佳的受试者被随机分配接受三种剂量的达格列净之一（2.5mg，n=137; 5 mg，n=137;或10 mg，n=135）或安慰剂（n=137）每日口服一次。随机化由计算机生成，并按研究中心分层，采用基于电话的中央交互式语音应答系统实施。患者继续接受研究前二甲双胍给药。主要结局是24周时血红蛋白A（1c）（HbA（1c））较基线的变化。所有接受至少一剂双盲研究药物且具有基线和至少一个基线后测量值（末次观察值结转）的随机化患者均纳入分析。采用ANCOVA模型对数据进行分析。该试验在ClinicalTrials.gov注册，编号NCT 00528879。结果534例患者纳入主要终点分析（达格列净2.5 mg，n=135;达格列净5 mg，n=133;达格列净10 mg，n=132;安慰剂，n=134）。第24周时，安慰剂组的平均HbA（1c）降低了-0-30%（95% CI -0.44至-0.16），而达格列净2.5 mg组为-0.67%（-0.81至-0.53，p=0-0002），达格列净2.5 mg组为-0.70%（-0.85至-0.56，p =0-0002），
Background Correction of hyperglycaemia and prevention of glucotoxicity are important objectives in the management of type 2 diabetes. Dapagliflozin, a selective sodium-glucose cotransporter-2 inhibitor, reduces renal glucose reabsorption in an insulin-independent manner. We assessed the efficacy and safety of dapagliflozin in patients who have inadequate glycaemic control with metformin.Methods In this phase 3, multicentre, double-blind, parallel-group, placebo-controlled trial, 546 adults with type 2 diabetes who were receiving daily metformin (>= 1500 mg per day) and had inadequate glycaemic control were randomly assigned to receive one of three doses of dapagliflozin (2.5 mg, n=137; 5 mg, n=137; or 10 mg, n=135) or placebo (n=137) orally once daily. Randomisation was computer generated and stratified by site, implemented with a central, telephone-based interactive voice response system. Patients continued to receive their pre-study metformin dosing. The primary outcome was change from baseline in haemoglobin A(1c) (HbA(1c)) at 24 weeks. All randomised patients who received at least one dose of double-blind study medication and who had both a baseline and at least one post-baseline measurement (last observation carried forward) were included in the analysis. Data were analysed by use of ANCOVA models. This trial is registered with ClinicalTrials.gov, number NCT00528879.Findings 534 patients were included in analysis of the primary endpoint (dapagliflozin 2.5 mg, n=135; dapagliflozin 5 mg, n=133; dapagliflozin 10 mg, n=132; placebo, n=134). At week 24, mean HbA(1c) had decreased by -0-30% (95% CI -0.44 to -0.16) in the placebo group, compared with -0.67% (-0.81 to -0.53, p=0-0002) in the dapagliflozin 2.5 mg group, -0.70% (-0.85 to -0.56, p