Budoff Matthew J, Davis Timothy M E, Palmer Alexandra G, Frederich Robert, Lawrence David E, Liu Jie, Gantz Ira, Derosa Giuseppe
Lundquist Institute, Torrance, CA, USA.
Medical School, University of Western Australia, Crawley, Australia.
Diabetes Ther. 2021 May;12(5):1279-1297. doi: 10.1007/s13300-021-01033-x. Epub 2021 Mar 15.
VERTIS CV is the cardiovascular outcome trial for the sodium-glucose cotransporter 2 (SGLT2) inhibitor ertugliflozin. A sub-study was conducted to assess the efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus (T2DM) inadequately glycemic-controlled on metformin and a sulfonylurea (SU).
Patients with T2DM, established atherosclerotic cardiovascular disease (ASCVD), and an HbA1c of 7.0-10.5% on stable metformin (≥ 1500 mg/day) and moderate to high SU doses were randomly assigned to once-daily ertugliflozin (5 or 15 mg) or placebo. The primary sub-study objectives were to assess the effect of ertugliflozin on HbA1c compared with placebo and to evaluate safety following 18 weeks of treatment. Key secondary endpoints included changes in fasting plasma glucose (FPG), body weight (BW), blood pressure (BP), and the proportion of patients achieving HbA1c < 7%.
Of the 8246 patients enrolled in VERTIS CV, 330 were eligible for this sub-study (ertugliflozin 5 mg, n = 100; ertugliflozin 15 mg, n = 113; placebo, n = 117). This subgroup had a mean (SD) age of 63.2 (8.4) years and T2DM duration of 11.4 (7.4) years. At week 18, ertugliflozin 5 mg and 15 mg were each associated with significantly greater least squares (LS) mean reductions from baseline in HbA1c relative to placebo (placebo-adjusted LS mean [95% CI] - 0.66% [- 0.89, - 0.43] and - 0.75% [- 0.98, - 0.53], respectively, p < 0.001 for each dose vs placebo). Ertugliflozin significantly reduced FPG and BW compared with placebo (p < 0.001), but not systolic BP. Adverse events were reported in 48.0%, 54.9%, and 47.0% of patients in the ertugliflozin 5 mg and 15 mg, and placebo groups. The incidences of symptomatic hypoglycemia were 11.0% (5 mg), 12.4% (15 mg), and 7.7% (placebo), and of severe hypoglycemia 2.0% (5 mg), 1.8% (15 mg), and 0.9% (placebo).
In patients with T2DM and ASCVD, ertugliflozin added to metformin and SU improved glycemic control, reduced BW, and was generally well tolerated.
VERTIS CV ClinicalTrials.gov identifier, NCT01986881.
VERTIS CV是一项针对钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂恩格列净的心血管结局试验。开展了一项子研究，以评估恩格列净在接受二甲双胍和磺脲类药物（SU）治疗但血糖控制不佳的2型糖尿病（T2DM）患者中的疗效和安全性。
患有T2DM、已确诊动脉粥样硬化性心血管疾病（ASCVD）且在稳定服用二甲双胍（≥1500毫克/天）和中高剂量SU的情况下糖化血红蛋白（HbA1c）为7.0-10.5%的患者被随机分配至每日一次的恩格列净（5或15毫克）或安慰剂组。子研究的主要目标是评估与安慰剂相比恩格列净对HbA1c的影响，并在治疗18周后评估安全性。关键次要终点包括空腹血糖（FPG）、体重（BW）、血压（BP）的变化以及HbA1c＜7%的患者比例。
在VERTIS CV纳入的8246例患者中，330例符合该子研究的条件（恩格列净5毫克组，n = 100；恩格列净15毫克组，n = 113；安慰剂组，n = 117）。该亚组患者的平均（标准差）年龄为63.2（8.4）岁，T2DM病程为11.4（7.4）年。在第18周时，与安慰剂相比，恩格列净5毫克和15毫克组的HbA1c从基线的最小二乘（LS）平均降幅均显著更大（安慰剂调整后的LS平均降幅[95%置信区间]分别为-0.66%[-0.89，-0.43]和-0.75%[-0.98，-0.53]，各剂量组与安慰剂组相比p均＜0.001）。与安慰剂相比，恩格列净显著降低了FPG和BW（p＜0.001），但未降低收缩压。恩格列净5毫克组、15毫克组和安慰剂组分别有48.0%、54.9%和47.0%的患者报告了不良事件。症状性低血糖的发生率分别为11.0%（5毫克组）、12.4%（15毫克组）和7.7%（安慰剂组），严重低血糖的发生率分别为2.0%（5毫克组）、1.8%（15毫克组）和0.9%（安慰剂组）。
在患有T2DM和ASCVD的患者中，在二甲双胍和SU基础上加用恩格列净可改善血糖控制、降低BW，且总体耐受性良好。
VERTIS CV，ClinicalTrials.gov标识符，NCT01986881。
