Dapagliflozin Is Effective as Add-on Therapy to Sitagliptin With or Without Metformin: A 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study
Dapagliflozin Is Effective as Add-on Therapy to Sitagliptin With or Without Metformin: A 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study
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DOI：
10.2337/dc13-0467
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发表时间：
2014-03-01
期刊：
影响因子：
16.2
通讯作者：
Parikh, Shamik
中科院分区：
文献类型：
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作者：
Jabbour, Serge A.;Hardy, Elise;Parikh, Shamik
目的 评估达格列净作为附加疗法对二肽基肽酶 4 抑制剂加或不加二甲双胍控制效果不佳的 2 型糖尿病患者的疗效和安全性。 研究设计和方法 在这项为期 24 周、多中心、随机、双盲、安慰剂对照、平行组、3 期研究中，432 名患者被随机分组，接受 24 周盲法延长期。接受达格列净 10 mg/天或在西格列汀 (100 mg/天) 二甲双胍 (1,500 mg/天) 中加入安慰剂。结果 达格列净组的基线 HbA(1c) 和 FPG 水平分别为 7.9% (63.0 mmol/mol) 和 162.2 mg/dL (9.0 mmol/L)，达格列净组为 8.0% (64.0 mmol/mol) 和安慰剂 163 mg/dL (9.0 mmol/L)。第 24 周时，与安慰剂 (0.0% [+0.4 mmol/mol]) 相比，达格列净显着降低平均 HbA(1c) 水平 (-0.5% [-4.9 mmol/mol])。与安慰剂相比，达格列净降低了基线值 8.0%（-0.8% [8.7 mmol/mol] 和 0.0% [0.3 mmol/mol]）和空腹血糖水平（-24.1 mg/dL [-1.3 mmol/L] 和 3.8 mg/dL [0.2] 的患者体重和 HbA(1c) 水平。毫摩尔/升]）。当按背景治疗对数据进行分层时，观察到类似的结果。第 24 周观察到的血糖和体重获益一直维持到第 48 周。第 8 周时收缩压相对于基线的变化在治疗组之间没有显着差异。在 48 周内，与安慰剂相比，接受达格列净治疗的患者因未能达到血糖目标而停药或获救的患者较少。各组之间的不良事件是平衡的，且停药率较低。第 48 周时，达格列净组 (9.8%) 比安慰剂组 (0.4%) 更常见提示生殖器感染的体征和症状。提示尿路感染的体征和症状在达格列净 (6.7%) 和安慰剂 (6.2%) 之间是平衡的。结论这些结果表明，对于西格列汀联合或不联合二甲双胍治疗效果不佳的 2 型糖尿病患者，达格列净的附加治疗可提供额外的临床益处，并且耐受性良好。
OBJECTIVETo assess the efficacy and safety of dapagliflozin as add-on therapy in patients with type 2 diabetes who were inadequately controlled with a dipeptidyl peptidase-4 inhibitor with or without metformin.RESEARCH DESIGN AND METHODSIn this 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 study with a 24-week blinded extension period, 432 patients were randomized to receive dapagliflozin 10 mg/day or placebo added to sitagliptin (100 mg/day) metformin (1,500 mg/day).RESULTSBaseline HbA(1c) and FPG levels were 7.9% (63.0 mmol/mol) and 162.2 mg/dL (9.0 mmol/L) for the dapagliflozin group and 8.0% (64.0 mmol/mol) and 163 mg/dL (9.0 mmol/L) for placebo. At week 24, dapagliflozin significantly reduced mean HbA(1c) levels (-0.5% [-4.9 mmol/mol]) versus placebo (0.0% [+0.4 mmol/mol]). Dapagliflozin reduced body weight versus placebo (-2.1 and -0.3 kg) and reduced HbA(1c) levels in patients with baseline values 8.0% (-0.8% [8.7 mmol/mol] and 0.0% [0.3 mmol/mol]) and fasting plasma glucose levels (-24.1 mg/dL [-1.3 mmol/L] and 3.8 mg/dL [0.2 mmol/L]). Similar results were observed when data were stratified by background therapy. Glycemic and weight benefits observed at week 24 were maintained through week 48. Changes from baseline in systolic blood pressure at week 8 were not significantly different between treatment groups. Over 48 weeks, fewer patients receiving dapagliflozin were discontinued or rescued for failing to achieve glycemic targets compared with placebo. Adverse events were balanced between groups, and discontinuation rates were low. At week 48, signs and symptoms suggestive of genital infection were more frequent with dapagliflozin (9.8%) than with placebo (0.4%). Signs and symptoms suggestive of urinary tract infection were balanced between dapagliflozin (6.7%) and placebo (6.2%).CONCLUSIONSThese results suggest that in patients with type 2 diabetes, inadequately controlled on sitagliptin with or without metformin, add-on treatment with dapagliflozin provides additional clinical benefit and is well tolerated.