Diabetes-Zentrum, Quakenbrück, Germany
Spitalul Clinic Judetean de Urgenta Constanta, Constanta, Romania.
Diabetes Care. 2015 Nov;38(11):2018-24. doi: 10.2337/dc15-0811. Epub 2015 Aug 31.
The objective of this study was to assess the efficacy and safety of triple therapy with saxagliptin add-on versus placebo add-on to dapagliflozin plus metformin in adults with type 2 diabetes.
Patients on stable metformin (≥1,500 mg/day) for ≥8 weeks with glycated hemoglobin (HbA1c) 8.0-11.5% (64-102 mmol/mol) at screening received open-label dapagliflozin (10 mg/day) plus metformin immediate release (IR) for 16 weeks. Patients with inadequate glycemic control (HbA1c 7-10.5% [53-91 mmol/mol]) were then randomized to receive placebo (n = 153) or saxagliptin 5 mg/day (n = 162) in addition to background dapagliflozin plus metformin IR. The primary efficacy end point was change in HbA1c from baseline to week 24.
There was a significantly greater reduction in HbA1c at 24 weeks with saxagliptin add-on (-0.51% [-5.6 mmol/mol]) versus placebo (-0.16% [-1.7 mmol/mol]) add-on to dapagliflozin plus metformin (difference, -0.35% [95% CI -0.52% to -0.18%] and -3.8 [-5.7 to -2.0 mmol/mol], respectively; P < 0.0001). Reductions in fasting plasma glucose and 2-h postprandial glucose were similar between treatment arms. A larger proportion of patients achieved HbA1c <7% (53 mmol/mol) with saxagliptin add-on (35.3%) versus placebo add-on (23.1%) to dapagliflozin plus metformin. Adverse events were similar between treatment groups. Episodes of hypoglycemia were infrequent in both treatment arms, and there were no episodes of major hypoglycemia.
Triple therapy with the addition of saxagliptin to dapagliflozin plus metformin was well tolerated and produced significant improvements in HbA1c in patients with type 2 diabetes inadequately controlled with dapagliflozin plus metformin.
本研究旨在评估在二甲双胍联合达格列净血糖控制不佳的患者中，加用沙格列汀与安慰剂相比，联合达格列净二甲双胍治疗的疗效和安全性。
筛选时，接受稳定剂量二甲双胍（≥1500mg/天）治疗≥8 周且糖化血红蛋白（HbA1c）为 8.0-11.5%（64-102mmol/mol）的患者接受为期 16 周的开放标签达格列净（10mg/天）联合二甲双胍速释片治疗。对于血糖控制仍不达标（HbA1c7-10.5%[53-91mmol/mol]）的患者，随机接受安慰剂（n=153）或沙格列汀 5mg/天（n=162）加用背景下的达格列净联合二甲双胍速释片治疗。主要疗效终点为治疗 24 周时 HbA1c 较基线的变化。
与安慰剂加用相比，加用沙格列汀可显著降低 HbA1c（-0.51%[-5.6mmol/mol]），而安慰剂加用则降低（-0.16%[-1.7mmol/mol]）（差值分别为-0.35%[95%CI-0.52%至-0.18%]和-3.8[-5.7 至-2.0mmol/mol]；P<0.0001）。治疗组之间空腹血糖和 2 小时餐后血糖的降低相似。加用沙格列汀可使更多患者达到 HbA1c<7%（53mmol/mol）（35.3%），而安慰剂加用则为（23.1%）（P<0.0001）。两组的不良事件相似。两种治疗方案的低血糖事件均不常见，且均无严重低血糖事件发生。
在二甲双胍联合达格列净血糖控制不佳的患者中，加用沙格列汀可耐受良好，并且可显著改善 HbA1c。
