Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX
Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT.
Diabetes Care. 2014 Jul;37(7):1815-23. doi: 10.2337/dc13-3055. Epub 2014 Jun 14.
We investigated the efficacy and safety of the sodium glucose cotransporter 2 inhibitor, empagliflozin, added to multiple daily injections of insulin (MDI insulin) in obese patients with type 2 diabetes mellitus (T2DM).
Patients inadequately controlled on MDI insulin ± metformin (mean HbA1c 8.3% [67 mmol/mol]; BMI 34.8 kg/m(2); insulin dose 92 international units/day) were randomized and treated with once-daily empagliflozin 10 mg (n = 186), empagliflozin 25 mg (n = 189), or placebo (n = 188) for 52 weeks. Insulin dose was to remain stable in weeks 1-18, adjusted to meet glucose targets in weeks 19-40, then stable in weeks 41-52. The primary end point was change from baseline in HbA1c at week 18. Secondary end points were changes from baseline in insulin dose, weight, and HbA1c at week 52.
Adjusted mean ± SE changes from baseline in HbA1c were -0.50 ± 0.05% (-5.5 ± 0.5 mmol/mol) for placebo versus -0.94 ± 0.05% (-10.3 ± 0.5 mmol/mol) and -1.02 ± 0.05% (-11.1 ± 0.5 mmol/mol) for empagliflozin 10 mg and empagliflozin 25 mg, respectively, at week 18 (both P < 0.001). At week 52, further reductions with insulin titration resulted in changes from baseline in HbA1c of -0.81 ± 0.08% (-8.9 ± 0.9 mmol/mol), -1.18 ± 0.08% (-12.9 ± 0.9 mmol/mol), and -1.27 ± 0.08% (-13.9 ± 0.9 mmol/mol) with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively, and final HbA1c of 7.5% (58 mmol/mol), 7.2% (55 mmol/mol), and 7.1% (54 mmol/mol), respectively. More patients attained HbA1c <7% (<53 mmol/mol) with empagliflozin (31-42%) versus placebo (21%; both P < 0.01). Empagliflozin 10 mg and empagliflozin 25 mg reduced insulin doses (-9 to -11 international units/day) and weight (-2.4 to -2.5 kg) versus placebo (all P < 0.01) at week 52.
In obese, difficult-to-treat patients with T2DM inadequately controlled on high MDI insulin doses, empagliflozin improved glycemic control and reduced weight without increasing the risk of hypoglycemia and with lower insulin requirements.
我们旨在研究钠-葡萄糖共转运蛋白 2 抑制剂恩格列净（empagliflozin）在接受多次胰岛素每日注射（MDI 胰岛素）治疗但血糖控制仍不佳的肥胖 2 型糖尿病（T2DM）患者中的疗效和安全性。
在接受 MDI 胰岛素±二甲双胍治疗但血糖控制仍不佳的患者（平均 HbA1c 8.3%[67 mmol/mol]；BMI 34.8 kg/m2；胰岛素剂量 92 国际单位/天）中，我们进行了一项随机对照试验，将患者分为恩格列净 10 mg 组（n=186）、恩格列净 25 mg 组（n=189）和安慰剂组（n=188），接受为期 52 周的治疗。在第 1-18 周期间，胰岛素剂量保持稳定，在第 19-40 周期间根据血糖目标进行调整，然后在第 41-52 周期间保持稳定。主要终点为第 18 周时与基线相比的 HbA1c 变化。次要终点为第 52 周时与基线相比的胰岛素剂量、体重和 HbA1c 变化。
与安慰剂组相比，恩格列净 10 mg 和 25 mg 组分别使 HbA1c 从基线降低了-0.50 ± 0.05%（-5.5 ± 0.5 mmol/mol）和-0.94 ± 0.05%（-10.3 ± 0.5 mmol/mol）和-1.02 ± 0.05%（-11.1 ± 0.5 mmol/mol），差异均有统计学意义（均 P<0.001）。在第 52 周时，随着胰岛素剂量的滴定，与安慰剂组相比，恩格列净 10 mg 和 25 mg 组的 HbA1c 进一步降低，分别为-0.81 ± 0.08%（-8.9 ± 0.9 mmol/mol）、-1.18 ± 0.08%（-12.9 ± 0.9 mmol/mol）和-1.27 ± 0.08%（-13.9 ± 0.9 mmol/mol），最终的 HbA1c 分别为 7.5%（58 mmol/mol）、7.2%（55 mmol/mol）和 7.1%（54 mmol/mol）。与安慰剂组（21%）相比，恩格列净组（31%-42%）有更多患者达到 HbA1c<7%（<53 mmol/mol），差异均有统计学意义（均 P<0.01）。与安慰剂组相比，恩格列净 10 mg 和 25 mg 组在第 52 周时分别减少了 9 至 11 个国际单位/天的胰岛素剂量和 2.4 至 2.5 kg 的体重，差异均有统计学意义（均 P<0.01）。
在接受高剂量 MDI 胰岛素治疗但血糖仍控制不佳的肥胖、治疗难度较大的 T2DM 患者中，恩格列净改善了血糖控制，减轻了体重，同时没有增加低血糖的风险，且胰岛素需求降低。
