VA San Diego Healthcare System Research Service and University of California San Diego School of Medicine, San Diego, CA, USA.
Int J Clin Pract. 2012 May;66(5):446-56. doi: 10.1111/j.1742-1241.2012.02911.x. Epub 2012 Mar 13.
Combining metformin (XR) with dapagliflozin to initiate pharmacotherapy in patients with type 2 diabetes (T2D) and high baseline HbA1c may be advantageous. We conducted two randomised, double-blind, three-arm 24-week trials in treatment-naïve patients to compare dapagliflozin plus metformin, dapagliflozin alone and metformin alone.
Eligible patients had baseline HbA1c 7.5-12%. Each trial had three arms: dapagliflozin plus metformin, dapagliflozin monotherapy and metformin monotherapy. Dapagliflozin in combination and as monotherapy was dosed at 5 mg (Study 1) and 10 mg (Study 2). Metformin in combination and as monotherapy was titrated to 2000 mg. The primary endpoint was HbA1c change from baseline; secondary endpoints included change in fasting plasma glucose (FPG) and weight.
In both trials, combination therapy led to significantly greater reductions in HbA1c compared with either monotherapy: -2.05 for dapagliflozin + metformin, -1.19 for dapagliflozin, and -1.35 for metformin (p < 0.0001) (Study 1); -1.98 for dapagliflozin + metformin, -1.45 for dapagliflozin and -1.44 for metformin (p < 0.0001) (Study 2). Combination therapy was statistically superior to monotherapy in reduction of FPG (p < 0.0001 for both studies); combination therapy was more effective than metformin for weight reduction (p < 0.0001). Dapagliflozin 10 mg was non-inferior to metformin in reducing HbA1c (Study 2). Events suggestive of genital infection were reported in 6.7%, 6.9% and 2.0% (Study 1) and 8.5%, 12.8% and 2.4% (Study 2) of patients in combination, dapagliflozin and metformin groups; events suggestive of urinary tract infection were reported in 7.7%, 7.9% and 7.5% (Study 1) and 7.6%, 11.0% and 4.3% (Study 2) of patients in the respective groups. No major hypoglycaemia was reported.
In treatment-naïve patients with T2D, dapagliflozin plus metformin was generally well tolerated and effective in reducing HbA1c, FPG and weight. Dapagliflozin-induced glucosuria led to an increase in events suggestive of urinary tract and genital infections.
在基线糖化血红蛋白（HbA1c）较高的 2 型糖尿病（T2D）患者中，起始联合二甲双胍（XR）和达格列净的药物治疗可能具有优势。我们开展了两项随机、双盲、三臂、为期 24 周的试验，比较了达格列净联合二甲双胍、达格列净单药治疗和二甲双胍单药治疗。
符合条件的患者基线 HbA1c 为 7.5-12%。每个试验均有 3 个治疗臂：达格列净联合二甲双胍、达格列净单药治疗和二甲双胍单药治疗。达格列净联合治疗和单药治疗剂量分别为 5 mg（研究 1）和 10 mg（研究 2）。二甲双胍联合治疗和单药治疗剂量滴定至 2000 mg。主要终点为基线时 HbA1c 的变化；次要终点包括空腹血糖（FPG）和体重的变化。
在两项试验中，与单药治疗相比，联合治疗均显著降低 HbA1c：达格列净+二甲双胍组 -2.05，达格列净组 -1.19，二甲双胍组 -1.35（p＜0.0001）（研究 1）；达格列净+二甲双胍组 -1.98，达格列净组 -1.45，二甲双胍组 -1.44（p＜0.0001）（研究 2）。联合治疗在降低 FPG 方面优于单药治疗（两项研究均 p＜0.0001）；与二甲双胍相比，联合治疗更有效降低体重（p＜0.0001）。达格列净 10 mg 在降低 HbA1c 方面不劣于二甲双胍（研究 2）。分别有 6.7%、6.9%和 2.0%（研究 1）以及 8.5%、12.8%和 2.4%（研究 2）的患者报告了联合治疗、达格列净和二甲双胍组出现疑似生殖器感染的事件；分别有 7.7%、7.9%和 7.5%（研究 1）以及 7.6%、11.0%和 4.3%（研究 2）的患者报告了各自组出现疑似尿路感染的事件。未报告严重低血糖事件。
在初治的 2 型糖尿病患者中，达格列净联合二甲双胍通常具有良好的耐受性，可有效降低 HbA1c、FPG 和体重。达格列净诱导的葡萄糖尿导致疑似尿路感染和生殖器感染事件的发生率增加。
