Hollander Priscilla, Liu Jie, Hill Julie, Johnson Jeremy, Jiang Zhi Wei, Golm Gregory, Huyck Susan, Terra Steven G, Mancuso James P, Engel Samuel S, Lauring Brett
Baylor Endocrine Center, Dallas, TX, USA.
Merck & Co., Inc., Kenilworth, NJ, USA.
Diabetes Ther. 2018 Feb;9(1):193-207. doi: 10.1007/s13300-017-0354-4. Epub 2017 Dec 27.
This study assessed the safety and efficacy of ertugliflozin (an oral sodium-glucose cotransporter 2 inhibitor) vs. glimepiride in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin.
This phase III, double-blind, non-inferiority study (NCT01999218) randomized patients with HbA1c ≥ 7.0% and ≤ 9.0% on stable metformin ≥ 1500 mg/day 1:1:1 to ertugliflozin 15 or 5 mg once-daily (QD), or glimepiride (titrated from 1 mg QD). The primary hypothesis was that ertugliflozin 15 mg was non-inferior to glimepiride on HbA1c (non-inferiority criterion: upper bound of the 95% confidence interval [CI] about the treatment difference < 0.3%).
Mean baseline HbA1c of randomized patients (N = 1326) was 7.8%. Mean and median doses of glimepiride were 3.0 mg/day throughout the study. At week 52, the least squares mean change (95% CI) from baseline in HbA1c was - 0.6% (- 0.7, - 0.5), - 0.6% (- 0.6, - 0.5), and - 0.7% (- 0.8, - 0.7) in the ertugliflozin 15 mg, ertugliflozin 5 mg, and glimepiride groups, respectively. The between-group difference for ertugliflozin 15 mg and glimepiride of 0.1% (- 0.0, 0.2) met the pre-specified non-inferiority criterion. Relative to glimepiride, greater body weight and systolic blood pressure (SBP) reductions were observed with ertugliflozin. The overall incidence of adverse events (AEs) was similar across groups. The incidence of symptomatic hypoglycemia and genital mycotic infection (GMI) were, respectively, lower and higher with ertugliflozin relative to glimepiride. The incidences of urinary tract infection and hypovolemia AEs were not meaningfully different among the groups.
Ertugliflozin 15 mg was non-inferior to glimepiride in reducing HbA1c when added to metformin in patients with T2DM. Ertugliflozin had an acceptable safety profile and resulted in less hypoglycemia and more GMIs than glimepiride.
Clinicaltrials.gov NCT01999218.
本研究评估了依鲁格列净（一种口服钠-葡萄糖协同转运蛋白2抑制剂）与格列美脲相比，在二甲双胍治疗控制不佳的2型糖尿病（T2DM）患者中的安全性和疗效。
这项III期双盲非劣效性研究（NCT01999218）将糖化血红蛋白（HbA1c）≥7.0%且≤9.0%、稳定服用二甲双胍≥1500mg/天的患者按1:1:1随机分为依鲁格列净15mg或5mg每日一次（QD）组，或格列美脲组（从1mg QD开始滴定）。主要假设是依鲁格列净15mg在HbA1c方面不劣于格列美脲（非劣效性标准：治疗差异的95%置信区间[CI]上限<0.3%）。
随机分组患者（N = 1326）的平均基线HbA1c为7.8%。整个研究期间格列美脲的平均和中位剂量为3.0mg/天。在第52周时，依鲁格列净15mg组、依鲁格列净5mg组和格列美脲组HbA1c自基线的最小二乘均值变化（95%CI）分别为-0.6%（-0.7，-0.5）、-0.6%（-0.6，-0.5）和-0.7%（-0.8，-0.7）。依鲁格列净15mg与格列美脲的组间差异为0.1%（-0.0，0.2），符合预先设定的非劣效性标准。与格列美脲相比，依鲁格列净使体重和收缩压（SBP）降低更多。各组不良事件（AE）的总体发生率相似。依鲁格列净导致的症状性低血糖发生率低于格列美脲，而生殖器真菌感染（GMI）发生率高于格列美脲。各组间尿路感染和低血容量性AE的发生率无显著差异。
在T2DM患者中，依鲁格列净15mg与二甲双胍联合使用时，在降低HbA1c方面不劣于格列美脲。依鲁格列净具有可接受的安全性，与格列美脲相比，低血糖发生率更低，GMI发生率更高。
Clinicaltrials.gov NCT01999218
