Department of Nephrology.
Second Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration Hospital.
J Hypertens. 2021 Apr 1;39(4):749-758. doi: 10.1097/HJH.0000000000002690.
Sodium-glucose co-transporter 2 (SGLT-2) inhibitors reduce the incidence of heart failure and death in patients with type-2 diabetes mellitus. Arterial stiffness is a prominent risk factor for heart failure and overall mortality. The aim of this study was to evaluate the effects of dapagliflozin on ambulatory brachial and central blood pressure (BP) levels and arterial stiffness parameters in patients with type-2 diabetes mellitus.
This is a double-blind, randomized, placebo-controlled clinical trial including 85 adult patients with type-2 diabetes mellitus on monotherapy or combination therapy with two of: metformin, sulphonylurea, DPP-4 inhibitor, or insulin. Patients were randomized in a 1 : 1 ratio to oral dapagliflozin 10 mg per day or placebo for 12 weeks. Study participants underwent 24-h ambulatory BP monitoring with the Mobil-O-Graph NG monitor at baseline and study-end.
Baseline demographic, clinical and laboratory parameters were similar in the two groups. During follow-up, 24-h brachial SBP/DBP (129.0 ± 12.6/77.3 ± 7.3 vs. 123.2 ± 12.4/75.1 ± 6.4 mmHg; P < 0.001/P = 0.008) and central SBP/DBP (117.4 ± 10.5/78.9 ± 7.3 vs. 113.3 ± 8.8/77.3 ± 6.5 mmHg; P = 0.002/P = 0.047) significantly decreased in dapagliflozin but not in the placebo group. Corresponding reductions of 24-h brachial SBP (-5.8 ± 9.5 vs. -0.1 ± 8.7, P = 0.005) and central SBP (-4.1 ± 8.0 vs. -0.7 ± 7.8; P = 0.046) were greater with dapagliflozin than placebo. Twenty-four-hour heart-rate adjusted augmentation index significantly decreased with dapagliflozin and insignificantly with placebo. Importantly, there was a significant difference in change of estimated 24-h PWV (-0.16 ± 0.32 vs. 0.02 ± 0.27; P = 0.007) favoring dapagliflozin. In generalized linear mixed models including 24-h brachial SBP as a random covariate, the adjusted marginal means of delta 24-h central SBP and delta 24-h PWV were not significantly different between-groups.
Treatment with dapagliflozin significantly reduces ambulatory brachial and central BP levels and PWV in patients with type-2 diabetes mellitus. Improvement in these parameters may substantially contribute to the cardiovascular benefits of SGLT-2 inhibitors.
钠-葡萄糖协同转运蛋白 2（SGLT-2）抑制剂可降低 2 型糖尿病患者心力衰竭和死亡的发生率。动脉僵硬度是心力衰竭和全因死亡率的一个重要危险因素。本研究旨在评估达格列净对 2 型糖尿病患者的动态肱动脉和中心血压（BP）水平及动脉僵硬度参数的影响。
这是一项双盲、随机、安慰剂对照的临床试验，纳入了 85 例正在接受二甲双胍、磺脲类药物、DPP-4 抑制剂或胰岛素联合治疗或单药治疗的 2 型糖尿病患者。患者以 1:1 的比例随机分为每日口服达格列净 10mg 或安慰剂组，治疗 12 周。研究参与者在基线和研究结束时使用 Mobil-O-Graph NG 监测仪进行 24 小时动态血压监测。
两组患者的基线人口统计学、临床和实验室参数相似。随访期间，达格列净组 24 小时肱动脉 SBP/DBP（129.0±12.6/77.3±7.3 比 123.2±12.4/75.1±6.4mmHg；P<0.001/P=0.008）和中心 SBP/DBP（117.4±10.5/78.9±7.3 比 113.3±8.8/77.3±6.5mmHg；P=0.002/P=0.047）显著降低，但安慰剂组无显著变化。达格列净组 24 小时肱动脉 SBP（-5.8±9.5 比-0.1±8.7，P=0.005）和中心 SBP（-4.1±8.0 比-0.7±7.8；P=0.046）降幅大于安慰剂组。24 小时心率校正增强指数（augmentation index）显著降低，而安慰剂组无显著变化。重要的是，24 小时 PWV 的变化有显著差异（-0.16±0.32 比 0.02±0.27；P=0.007），达格列净组更优。在包括 24 小时肱动脉 SBP 作为随机协变量的广义线性混合模型中，组间的 24 小时中心 SBP 和 24 小时 PWV 的调整边缘均值无显著差异。
达格列净治疗可显著降低 2 型糖尿病患者的动态肱动脉和中心 BP 水平及 PWV。这些参数的改善可能对 SGLT-2 抑制剂的心血管获益有重要贡献。
