Kristensen Didde Kidmose, Mose Frank Holden, Buus Niels Henrik, Duus Camilla Lundgreen, Mårup Frederik Husum, Bech Jesper Nørgaard, Nielsen Steffen Flindt
University Clinic in Nephrology and Hypertension, Gødstrup Hospital, Herning, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark.
Diabetes Obes Metab. 2025 Mar;27(3):1123-1131. doi: 10.1111/dom.16097. Epub 2024 Nov 29.
The objective of this study was to examine the effects of empagliflozin on endothelium-dependent and endothelium-independent vasodilatation and systemic hemodynamic parameters and to assess the role of the nitric oxide (NO) system in patients with type 2 diabetes (T2DM).
In this double-blind, placebo-controlled cross over trial, patients with T2DM were treated with either empagliflozin 10 mg or matching placebo for 4 weeks. Following a 2-week washout, participants were crossed over to 4 weeks of the opposite treatment. Forearm blood flow (FBF) was measured after each treatment period using venous occlusion plethysmography. Acetylcholine and sodium nitroprusside (SNP) were infused into the brachial artery to assess endothelium-dependent and endothelium-independent vasodilatory function, respectively. Total peripheral resistance, 24-h blood pressure (BP) and biochemical markers of NO activity were measured as well.
Sixteen participants completed the trial. The mean age was 68 ± 8 years, and 69% were male. The SNP response increased by 21% (geometric mean ratio 1.21, 95% CI: 1.09; 1.33) during treatment with empagliflozin compared to placebo (p ≤ 0.001), but not during acetylcholine infusion (p = 0.290). Empagliflozin decreased 24-h systolic BP by 5 mmHg (95% CI: -9; -1 mmHg) (p = 0.015), diastolic BP by 2 mmHg (95% CI: -5; 0 mmHg) (p = 0.029) and systemic vascular resistance by 48 dyn×s/m (95% CI: -94; -1 dyn×s/m) (p = 0.044). Furthermore, empagliflozin reduced plasma levels of nitrite and urinary levels of NOx.
Empagliflozin improves endothelium-independent vasodilation, reduces vascular resistance and lowers 24-h BP in patients with T2DM, whereas no change in endothelial-dependent vasodilation was observed.
EU Clinical Trials Register number: 2019-004303-12 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004303-12/DK).
本研究旨在探讨恩格列净对2型糖尿病（T2DM）患者内皮依赖性和非内皮依赖性血管舒张及全身血流动力学参数的影响，并评估一氧化氮（NO）系统的作用。
在这项双盲、安慰剂对照的交叉试验中，T2DM患者接受10 mg恩格列净或匹配的安慰剂治疗4周。经过2周的洗脱期后，参与者交叉接受为期4周的相反治疗。在每个治疗期结束后，使用静脉阻塞体积描记法测量前臂血流量（FBF）。分别向肱动脉注入乙酰胆碱和硝普钠（SNP），以评估内皮依赖性和非内皮依赖性血管舒张功能。还测量了总外周阻力、24小时血压（BP）和NO活性的生化标志物。
16名参与者完成了试验。平均年龄为68±8岁，69%为男性。与安慰剂相比，恩格列净治疗期间SNP反应增加了21%（几何平均比1.21，95%CI：1.09；1.33）（p≤0.001），但在注入乙酰胆碱期间无变化（p=0.290）。恩格列净使24小时收缩压降低5 mmHg（95%CI：-9；-1 mmHg）（p=0.015），舒张压降低2 mmHg（95%CI：-5；0 mmHg）（p=0.029），全身血管阻力降低48 dyn×s/m（95%CI：-94；-1 dyn×s/m）（p=0.044）。此外，恩格列净降低了血浆亚硝酸盐水平和尿中NOx水平。
恩格列净可改善T2DM患者的非内皮依赖性血管舒张，降低血管阻力并降低24小时血压，而内皮依赖性血管舒张未见变化。
欧盟临床试验注册号：2019-004303-12（https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004303-12/DK）
