Lutnik Martin, Weisshaar Stefan, Litschauer Brigitte, Bayerle-Eder Michaela, Niederdöckl Jan, Wolzt Michael
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Department of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria.
Sci Rep. 2025 May 13;15(1):16633. doi: 10.1038/s41598-025-01405-4.
Ischemia-reperfusion injury (IRI) causes vascular endothelial dysfunction. Preclinical data suggest that the SGLT2 inhibitor dapagliflozin may protect against vascular IRI. This trial has investigated if oral treatment with dapagliflozin can mitigate the transient impairment of IRI-induced-endothelial dysfunction in the forearm resistance vasculature. 32 healthy males (n = 16 per group, age: 27 ± 4 yrs) were studied in this randomized, placebo-controlled, parallel-group, double-blinded trial. Acetylcholine (ACh; endothelium-dependent vasodilator) and glyceryltrinitrate (GTN; endothelium-independent vasodilator) were administered into the brachial artery of the non-dominant arm. The response to stepwise increasing doses on forearm blood flow (FBF) was assessed. FBF was measured before and after a cuff-induced 20-minute forearm ischemia at pre-dose and following daily intake of 10 mg dapagliflozin or placebo over 15 days. IRI reduced endothelium-dependent vasodilatation by 29% (p < 0.001, paired t-test). After a 15-day treatment period, IRI-induced endothelial dysfunction was abrogated in participants receiving dapagliflozin (FBF ACh ratios post- vs. pre-ischemia: dapagliflozin: 0.93; 95% CI: 0.80-1.29) but unchanged with placebo (0.81; 95% CI: 0.68-0.92; p = 0.015 vs. pre-ischemia). GTN-induced vasodilation was not altered by IRI or treatment. Dapagliflozin treatment at standard clinical doses over 15 days prevents IRI-induced vascular endothelial dysfunction in the forearm resistance vasculature of healthy young males. The underlying mechanism and the potential clinical impact remain to be demonstrated.Clinical trial registration https://clinicaltrials.gov/study/NCT05217654 NCT05217654; EudraCT number: 2021-005002-95 Date of registration: 20/01/2022.
缺血再灌注损伤（IRI）会导致血管内皮功能障碍。临床前数据表明，钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂达格列净可能对血管IRI具有保护作用。本试验研究了口服达格列净治疗是否能减轻IRI诱导的前臂阻力血管内皮功能障碍的短暂损害。在这项随机、安慰剂对照、平行组、双盲试验中，对32名健康男性（每组n = 16，年龄：27±4岁）进行了研究。将乙酰胆碱（ACh；内皮依赖性血管舒张剂）和硝酸甘油（GTN；非内皮依赖性血管舒张剂）注入非优势臂的肱动脉。评估前臂血流量（FBF）对逐步增加剂量的反应。在预给药时以及在每天服用10 mg达格列净或安慰剂15天后，在袖带诱导的20分钟前臂缺血前后测量FBF。IRI使内皮依赖性血管舒张降低了29%（p < 0.001，配对t检验）。经过15天的治疗期后，接受达格列净治疗的参与者中IRI诱导的内皮功能障碍得到消除（缺血后与缺血前的FBF ACh比值：达格列净：0.93；95%CI：0.80 - 1.29），但安慰剂组无变化（0.81；95%CI：0.68 - 0.92；与缺血前相比p = 0.015）。IRI或治疗未改变GTN诱导的血管舒张。在健康年轻男性的前臂阻力血管中，15天的标准临床剂量达格列净治疗可预防IRI诱导的血管内皮功能障碍。其潜在机制和临床影响仍有待证实。临床试验注册https://clinicaltrials.gov/study/NCT05217654 NCT05217654；欧盟临床试验编号：2021 - 005002 - 95 注册日期：2022年1月20日。
