Miller Sam, Krumins Tania, Zhou Haojin, Huyck Susan, Johnson Jeremy, Golm Gregory, Terra Steven G, Mancuso James P, Engel Samuel S, Lauring Brett
SAM Clinical Research Center, San Antonio, TX, USA.
Merck & Co., Inc., Kenilworth, NJ, USA.
Diabetes Ther. 2018 Feb;9(1):253-268. doi: 10.1007/s13300-017-0358-0. Epub 2018 Jan 8.
Ertugliflozin is an oral sodium-glucose cotransporter 2 inhibitor that is being developed to treat type 2 diabetes mellitus (T2DM). This study assessed the efficacy and safety of co-initiation of ertugliflozin and sitagliptin compared with placebo in patients with T2DM inadequately controlled on diet and exercise.
In this phase III, randomized, double-blind, multicenter, placebo-controlled 26-week study (NCT02226003), patients with T2DM and glycated hemoglobin (HbA1c) 8.0-10.5% on diet/exercise were randomized 1:1:1 to ertugliflozin 5 mg once daily (QD) and sitagliptin 100 mg QD (E5/S100), ertugliflozin 15 mg QD and sitagliptin 100 mg QD (E15/S100), or placebo. The primary efficacy endpoint was the change from baseline in HbA1c at week 26.
The mean baseline HbA1c of the randomized patients (n = 291) was 8.9%. At week 26, both ertugliflozin/sitagliptin treatments provided significant reductions from baseline in HbA1c compared with placebo [least squares mean HbA1c change (95% confidence intervals) from baseline was - 0.4% (- 0.7, - 0.2), - 1.6% (- 1.8, - 1.4), and - 1.7% (- 1.9, - 1.5) for placebo, E5/S100, and E15/S100, respectively]. At week 26, 8.3%, 35.7%, and 31.3% of patients receiving placebo, E5/S100, and E15/S100, respectively, had HbA1c < 7.0%. Significant reductions in fasting plasma glucose, 2-h post-prandial glucose, body weight, and systolic blood pressure were observed with both ertugliflozin/sitagliptin groups compared with placebo. The incidence of adverse events (AEs) was similar across the groups. The incidences of the pre-specified AEs of urinary tract infection, genital mycotic infection, symptomatic hypoglycemia, and hypovolemia were low and not meaningfully different across groups.
Co-initiation of ertugliflozin with sitagliptin in patients with T2DM inadequately controlled on diet and exercise provided a clinically meaningful improvement in glycemic control over 26 weeks.
Clinicaltrials.gov NCT02226003.
依鲁格列净是一种口服钠-葡萄糖协同转运蛋白2抑制剂，正在开发用于治疗2型糖尿病（T2DM）。本研究评估了在饮食和运动控制不佳的T2DM患者中，与安慰剂相比，联合起始使用依鲁格列净和西格列汀的疗效和安全性。
在这项III期、随机、双盲、多中心、安慰剂对照的26周研究（NCT02226003）中，饮食/运动控制下糖化血红蛋白（HbA1c）为8.0-10.5%的T2DM患者按1:1:1随机分组，分别接受每日一次5mg依鲁格列净和100mg西格列汀（E5/S100）、每日一次15mg依鲁格列净和100mg西格列汀（E15/S100）或安慰剂治疗。主要疗效终点是第26周时HbA1c相对于基线的变化。
随机分组患者（n = 291）的平均基线HbA1c为8.9%。在第26周时，与安慰剂相比，依鲁格列净/西格列汀两种治疗方案均使HbA1c从基线水平显著降低[安慰剂、E5/S100和E15/S100组从基线水平的HbA1c最小二乘均值变化（95%置信区间）分别为-0.4%（-0.7，-0.2）、-1.6%（-1.8，-1.4）和-1.7%（-1.9，-1.5）]。在第26周时，接受安慰剂、E5/S100和E15/S100治疗的患者中，HbA1c<7.0%的比例分别为8.3%、35.7%和31.3%。与安慰剂相比，依鲁格列净/西格列汀两组患者的空腹血糖、餐后2小时血糖、体重和收缩压均显著降低。各组不良事件（AE）的发生率相似。预先指定的尿路感染、生殖器真菌感染、症状性低血糖和血容量不足等AE的发生率较低，且各组之间无显著差异。
在饮食和运动控制不佳的T2DM患者中，联合起始使用依鲁格列净和西格列汀在26周内可实现临床上有意义的血糖控制改善。
Clinicaltrials.gov NCT02226003
