Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
British Heart Foundation, Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Diabetologia. 2018 Oct;61(10):2108-2117. doi: 10.1007/s00125-018-4670-7. Epub 2018 Aug 22.
Sodium-glucose cotransporter (SGLT)2 inhibitors have been demonstrated to reduce cardiovascular events, particularly heart failure, in cardiovascular outcome trials. Here, we review the proposed mechanistic underpinnings of this benefit. Specifically, we focus on the role of SGLT2 inhibitors in optimising ventricular loading conditions through their effect on diuresis and natriuresis, in addition to reducing afterload and improving vascular structure and function. Further insights into the role of SGLT2 inhibition in myocardial metabolism and substrate utilisation are outlined. Finally, we discuss two emerging themes: how SGLT2 inhibitors may regulate Na/H exchange at the level of the heart and kidney and how they may modulate adipokine production. The mechanistic discussion is placed in the context of completed and ongoing trials of SGLT2 inhibitors in the prevention and treatment of heart failure in individuals with and without diabetes.
钠-葡萄糖协同转运蛋白（SGLT）2 抑制剂已被证明可减少心血管事件，特别是心力衰竭，在心血管结局试验中。在这里，我们回顾了这种益处的拟议机制基础。具体来说，我们专注于 SGLT2 抑制剂通过利尿和排钠作用优化心室负荷条件的作用，除了降低后负荷和改善血管结构和功能。进一步深入了解 SGLT2 抑制在心肌代谢和底物利用中的作用。最后，我们讨论了两个新兴主题：SGLT2 抑制剂如何在心脏和肾脏水平调节 Na/H 交换，以及它们如何调节脂肪因子的产生。在有和没有糖尿病的个体中预防和治疗心力衰竭的 SGLT2 抑制剂的已完成和正在进行的试验背景下，对机制进行了讨论。
