Pfizer Worldwide Research and Development, Pfizer Inc, Cambridge, MA, USA.
TOTALL Diabetes Hormone Institute, Indore, India.
Diabetes Obes Metab. 2015 Jun;17(6):591-598. doi: 10.1111/dom.12460. Epub 2015 Mar 31.
To investigate the efficacy and safety of ertugliflozin, in a phase II dose-ranging study, in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin.
A total of 328 patients [mean T2DM duration, 6.3 years; mean glycated haemoglobin (HbA1c), 8.1%] were randomized to once-daily ertugliflozin (1, 5, 10, 25 mg), sitagliptin (100 mg) or placebo, for 12 weeks. The primary efficacy endpoint was change from baseline to week 12 in HbA1c concentration and the secondary efficacy endpoints were changes from baseline to week 12 in body weight, fasting plasma glucose (FPG) and systolic/diastolic blood pressure (SBP/DBP). Safety and tolerability were also monitored.
Ertugliflozin (1-25 mg/day) produced significant reductions in HbA1c concentration [placebo-corrected least-squares mean (LSM) -0.45% (1 mg) to -0.72% (25 mg); p ≤ 0.002, similar to sitagliptin (-0.76%; p = 0.0001)], FPG (LSM -1.17 to -1.90 mmol/l; p < 0.0001) and body weight (-1.15 to -2.15%; p < 0.0001). The LSM SBP decreased by -3.4 to -4.0 mmHg from baseline with ertugliflozin 5-25 mg/day. No reductions in body weight or blood pressure were observed with sitagliptin. After randomization, 2.7% of patients (9/328) withdrew because of adverse events (AEs); the frequency of AEs was evenly distributed across groups. No dose-related increase in AE frequency occurred with ertugliflozin. Hypoglycaemia was reported in 5 (1.5%) randomized participants (all in the ertugliflozin group). The frequency of urinary tract infection was 3.2% for ertugliflozin (pooled across groups), 1.8% for sitagliptin, 7.4% for placebo, and the frequency of genital fungal infections was 3.7% for ertugliflozin (pooled) versus 1.9% for placebo.
Ertugliflozin (1-25 mg/day) improved glycaemic control, body weight and blood pressure in patients with T2DM suboptimally controlled on metformin, and was well tolerated.
在一项 2 期剂量范围研究中，评估恩格列净在二甲双胍控制不佳的 2 型糖尿病（T2DM）患者中的疗效和安全性。
共纳入 328 例患者（平均 T2DM 病程 6.3 年；平均糖化血红蛋白（HbA1c）8.1%），随机接受每日一次恩格列净（1、5、10、25mg）、西格列汀（100mg）或安慰剂治疗 12 周。主要疗效终点为基线至 12 周时 HbA1c 浓度的变化，次要疗效终点为基线至 12 周时体重、空腹血糖（FPG）和收缩压/舒张压（SBP/DBP）的变化。同时监测安全性和耐受性。
恩格列净（1-25mg/天）可显著降低 HbA1c 浓度[安慰剂校正最小二乘均数（LSM）-0.45%（1mg）至-0.72%（25mg）；p≤0.002，与西格列汀（-0.76%；p=0.0001）相似]、FPG（LSM-1.17 至-1.90mmol/l；p<0.0001）和体重（LSM-1.15 至-2.15%；p<0.0001）。恩格列净 5-25mg/天治疗后 SBP 平均下降 3.4-4.0mmHg。西格列汀治疗组体重和血压无下降。随机分组后，有 2.7%（9/328）的患者因不良事件（AE）退出；各组 AE 发生率相当。恩格列净未出现与剂量相关的 AE 发生率增加。共有 5 例（1.5%）随机参与者发生低血糖（均为恩格列净组）。恩格列净组报告的低血糖发生率为 5（1.5%）例，西格列汀组为 1.8%，安慰剂组为 7.4%，恩格列净组尿路感染发生率为 3.2%（各组汇总），西格列汀组为 1.8%，安慰剂组为 7.4%，恩格列净组生殖器真菌感染发生率为 3.7%（各组汇总），安慰剂组为 1.9%。
恩格列净（1-25mg/天）可改善二甲双胍控制不佳的 T2DM 患者的血糖控制、体重和血压，且具有良好的耐受性。
