Suzuki Katsunori, Mitsuma Yurie, Sato Takaaki, Anraku Takumi, Hatta Mariko
Division of Endocrinology and Metabolism, Saiseikai Niigata Daini Hospital, Niigata, Japan.
Department of Nutrition, Saiseikai Niigata Daini Hospital, Niigata, Japan.
J Clin Med Res. 2016 Nov;8(11):805-814. doi: 10.14740/jocmr2741w. Epub 2016 Sep 29.
Some patients with type 2 diabetes mellitus (T2DM) on insulin have poor glycemic control and require add-on therapy to reach target glucose values. Increased insulin doses or the addition of an oral antidiabetic drug (OAD) may improve glycemic control, but many patients fail to achieve target values. The aim of this study was to compare the treatment efficacy and safety of three different therapies in such patients.
T2DM outpatients with poor glycemic control (HbA1c ≥ 7.0%) despite insulin therapy (including patients on OADs other than a sodium-glucose cotransporter 2 (SGLT2) inhibitor) were included. The patients had a body mass index (BMI) of ≥ 22 kg/m and an estimated glomerular filtration rate (eGFR) of ≥ 45 mL/min/1.73 m, did not have depletion of endogenous insulin, and had stable glucose levels for 3 months before study entry on insulin therapy. Treatment was continued for 24 weeks with insulin dose-increase therapy, tofogliflozin add-on therapy, or a combination of insulin glargine + tofogliflozin. The primary endpoints were HbA1c, weight, and total insulin dose. Secondary endpoints included fasting plasma glucose (FPG), blood pressure, lipid profiles, and incidence of adverse events.
At baseline, the participants' median age was 59.0 years, mean BMI was 28.7 kg/m, mean eGFR was 89.2 mL/min/1.73 m, mean HbA1c was 8.7%, and mean FPG was 174.1 mg/dL. The mean duration of insulin therapy was approximately 7 years. The mean daily insulin dose was approximately 40 U in the three groups. Overall, 85% received other background OADs in addition to insulin. Over the 24-week period, HbA1c in the insulin group decreased slightly initially and then plateaued; daily total insulin dose and weight increased, and blood pressure increased slightly. In the insulin + tofogliflozin group and the glargine + tofogliflozin group, HbA1c decreased greatly initially, and this continued over the 24-week period, with HbA1c decreases of -1.0% and -0.8%, respectively; total daily insulin dose (-2.6 and -12.7 U, respectively) and weight (-2.9 and -3.4 kg, respectively) decreased, and blood pressure decreased slightly. Tofogliflozin therapy was well tolerated.
Tofogliflozin may offer a new option for patients whose T2DM remains inadequately controlled on insulin therapy with or without additional oral glucose-lowering agents.
一些接受胰岛素治疗的2型糖尿病（T2DM）患者血糖控制不佳，需要加用其他治疗以达到血糖目标值。增加胰岛素剂量或加用口服降糖药（OAD）可能改善血糖控制，但许多患者仍无法达到目标值。本研究旨在比较三种不同治疗方案对此类患者的治疗效果和安全性。
纳入尽管接受胰岛素治疗（包括使用除钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂以外的OAD的患者）但血糖控制不佳（糖化血红蛋白[HbA1c]≥7.0%）的T2DM门诊患者。患者体重指数（BMI）≥22 kg/m²，估算肾小球滤过率（eGFR）≥45 mL/min/1.73 m²，内源性胰岛素未耗竭，且在开始胰岛素治疗前3个月血糖水平稳定。采用胰岛素剂量增加疗法、托格列净加用疗法或甘精胰岛素+托格列净联合疗法持续治疗24周。主要终点为HbA1c、体重和胰岛素总剂量。次要终点包括空腹血糖（FPG）、血压、血脂谱及不良事件发生率。
基线时，参与者的中位年龄为59.0岁，平均BMI为28.7 kg/m²，平均eGFR为89.2 mL/min/1.73 m²，平均HbA1c为8.7%，平均FPG为174.1 mg/dL。胰岛素治疗的平均时长约为7年。三组的平均每日胰岛素剂量约为40 U。总体而言，85%的患者除胰岛素外还接受了其他背景OAD治疗。在24周期间，胰岛素组的HbA1c最初略有下降，然后趋于平稳；每日胰岛素总剂量和体重增加，血压略有升高。在胰岛素+托格列净组和甘精胰岛素+托格列净组中，HbA1c最初大幅下降，并在24周期间持续下降，分别下降了-1.0%和-0.8%；每日胰岛素总剂量（分别为-2.6和-12.7 U）和体重（分别为-2.9和-3.4 kg）下降，血压略有下降。托格列净治疗耐受性良好。
对于接受或未接受额外口服降糖药治疗但胰岛素治疗仍无法充分控制T2DM的患者，托格列净可能提供一种新的选择。
