Sodium–glucose co-transporter-2 inhibitors or gliflozins, the newest anti-hyperglycemic class, induce cardioprotective benefits in patients with type 2 diabetes (T2D). As platelet activation and oxidative stress play a key role in atherothrombotic-related complications, we hypothesized that gliflozins might modulate oxidative stress, platelet activation and thrombus formation. We performed an interventional open-label single-arm before-after study in 32 T2D patients on top of their ongoing metformin therapy. The population was divided into two groups: treatment with GLP-1 receptor agonists (GLP-1RA, Group A) and gliflozins (Group B). Oxidative stress, platelet activation and thrombus growth were assessed before and after 15 days of treatment. Compared to the baseline, gliflozins treatment significantly decreased sNOX2-dp (−45.2%, p < 0.001), H₂O₂ production (−53.4%, p < 0.001), TxB2 (−33.1%, p < 0.001), sP-selectin (−49.3%, p < 0.001) and sCD40L levels (−62.3%, p < 0.001) as well as thrombus formation (−32%, p < 0.001), whereas it potentiated anti-oxidant power (HBA, +30.8%, p < 0.001). Moreover, a significant difference in oxidative stress, platelet activation and thrombus formation across groups A and B was found. In addition, an in vitro study on stimulated platelets treated with gliflozins (10–30 μM) showed a reduction in oxidative stress, platelet activation and thrombus growth. Our results showed that gliflozins have antiplatelet and antithrombic activity related to an NOX2 down-regulation, suggesting a new mechanism responsible for cardiovascular protection.

中文翻译：

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钠-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂通过降低与 NOX2 相关的氧化应激来减少血小板活化和血栓形成：一项初步研究

钠-葡萄糖协同转运蛋白 2 抑制剂或格列净是最新的抗高血糖药物，对 2 型糖尿病 (T2D) 患者具有心脏保护作用。由于血小板活化和氧化应激在动脉粥样硬化血栓形成相关并发症中起关键作用，我们假设格列净可能调节氧化应激、血小板活化和血栓形成。我们对 32 名 T2D 患者在正在进行的二甲双胍治疗的基础上进行了一项介入性开放标签单臂前后对比研究。人群分为两组：用 GLP-1 受体激动剂（GLP-1RA，A 组）和格列净（B 组）治疗。在治疗 15 天前后评估氧化应激、血小板活化和血栓生长。与基线相比，格列净治疗显着降低了 sNOX2-dp (−45.2%,p < 0.001)、H ₂ O ₂产生 (−53.4%, p < 0.001)、TxB2 (−33.1%, p < 0.001)、sP-选择素 (−49.3%, p < 0.001) 和 sCD40L 水平 (−62.3% , p < 0.001) 以及血栓形成 (-32%, p < 0.001), 而它增强了抗氧化能力 (HBA, +30.8%, p< 0.001)。此外，发现 A 组和 B 组在氧化应激、血小板活化和血栓形成方面存在显着差异。此外，一项关于用格列净 (10–30 μM) 处理的刺激血小板的体外研究表明，氧化应激、血小板活化和血栓生长均有所减少。我们的结果表明，格列净具有与 NOX2 下调相关的抗血小板和抗血栓活性，表明一种负责心血管保护的新机制。