恩格列净用于磺脲类单药治疗血糖控制不佳的糖尿病患者的疗效和安全性：VERTIS CV研究的一项子研究
Efficacy and Safety of Ertugliflozin in Patients With Diabetes Mellitus Inadequately Controlled by Sulfonylurea Monotherapy: a Substudy of VERTIS CV.
作者信息
Strojek Krzysztof, Pandey A Shekhar, Dell Vanessa, Sisson Melanie, Wang Shuai, Huyck Susan, Liu Jie, Gantz Ira
机构信息
Department of Internal Diseases, Diabetology and Cardiometabolic Diseases, Faculty of Medical Sciences Zabrze, Medical University of Silesia, Katowice, Poland.
Cambridge Cardiac Care Centre, Cambridge, ON, Canada.
出版信息
Diabetes Ther. 2021 Apr;12(4):1175-1192. doi: 10.1007/s13300-021-01018-w. Epub 2021 Mar 10.
INTRODUCTION
Sulfonylureas (SU) are commonly used antihyperglycemic agents. VERTIS CV was the cardiovascular outcome study for the sodium-glucose cotransporter 2 inhibitor ertugliflozin. Enrollment of patients in VERTIS CV occurred in two sequential cohorts (Cohort 1 and Cohort 2).
METHODS
This substudy assessed the efficacy and safety of adding ertugliflozin to SU monotherapy. The primary endpoint was the change in HbA1c from baseline at 18 weeks.
RESULTS
Among the 8246 patients who were randomized in VERTIS CV, 157 patients in Cohort 1 and 135 patients in Cohort 2 were on SU monotherapy at baseline. In the prespecified analysis (Cohort 1 only), the least squares (LS) mean HbA1c change from baseline for placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg was - 0.56%, - 0.91%, and - 0.78%, respectively (placebo-adjusted LS mean [95% CI] change: - 0.35% [- 0.72%, 0.02%]; - 0.22% [- 0.60%, 0.16%] for ertugliflozin 5 and 15 mg, respectively; p > 0.05 for both). In a post-hoc analysis that included Cohorts 1 and 2 (N = 292), the LS mean HbA1c change from baseline at week 18 for placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg was - 0.31%, - 0.77%, and - 0.68%, respectively (placebo-adjusted change: - 0.46% [- 0.73%, - 0.18%]; - 0.37% [- 0.66%, - 0.09%]; p = 0.001 and 0.01 for ertugliflozin 5 and 15 mg, respectively). In Cohort 1, adverse events were reported in 45.8%, 47.3%, and 25.9% of patients with placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg. The incidence rates of symptomatic hypoglycemia were 0.0%, 5.5%, and 3.7%, respectively, with no cases of severe hypoglycemia. The safety profile was similar for Cohorts 1 and 2 combined.
CONCLUSION
The addition of ertugliflozin to SU monotherapy reduced HbA1c but did not result in significant placebo-adjusted reductions from baseline according to the prespecified primary analysis (n = 157); however, in a post-hoc analysis with a larger patient population (n = 292), significant and clinically relevant HbA1c reductions were observed. Ertugliflozin was generally well tolerated.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT01986881.
引言
磺脲类药物（SU）是常用的降糖药物。VERTIS CV是关于钠-葡萄糖协同转运蛋白2抑制剂恩格列净的心血管结局研究。VERTIS CV研究中的患者入组分为两个连续队列（队列1和队列2）。
方法
本亚组研究评估了在SU单药治疗基础上加用恩格列净的疗效和安全性。主要终点是18周时糖化血红蛋白（HbA1c）相对于基线的变化。
结果
在VERTIS CV研究中随机分组的8246例患者中，队列1有157例患者、队列2有135例患者在基线时接受SU单药治疗。在预先设定的分析中（仅队列1），安慰剂组、5 mg恩格列净组和15 mg恩格列净组HbA1c相对于基线的最小二乘（LS）均值变化分别为-0.56%、-0.91%和-0.78%（安慰剂校正LS均值[95%置信区间]变化：-0.35%[-0.72%，0.02%]；5 mg和15 mg恩格列净组分别为-0.22%[-0.60%，0.16%]；两者p均>0.05）。在一项纳入队列1和队列2（N = 292）的事后分析中，安慰剂组、5 mg恩格列净组和15 mg恩格列净组在第18周时HbA1c相对于基线的LS均值变化分别为-0.31%、-0.77%和-0.68%（安慰剂校正变化：-0.46%[-0.73%，-0.18%]；-0.37%[-0.66%，-0.09%]；5 mg和15 mg恩格列净组p分别为0.001和0.01）。在队列1中，安慰剂组、5 mg恩格列净组和15 mg恩格列净组分别有45.8%、47.3%和25.9%的患者报告了不良事件。症状性低血糖的发生率分别为0.0% 、5.5%和3.7%，无严重低血糖病例。队列1和队列2合并后的安全性概况相似。
结论
在SU单药治疗基础上加用恩格列净可降低HbA1c，但根据预先设定的主要分析（n = 157），相对于基线，安慰剂校正后未出现显著降低；然而，在一项纳入更多患者的事后分析（n = 292）中，观察到HbA1c有显著且具有临床意义的降低。恩格列净总体耐受性良好。
试验注册
ClinicalTrials.gov标识符：NCT01986881。
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