Cardiology Department, Heraklion University Hospital, Crete, Greece.
Laboratory of Molecular Cardiology, University of Crete, School of Medicine, Crete, Greece.
Curr Vasc Pharmacol. 2022;20(2):178-188. doi: 10.2174/1570161120666211227125033.
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have changed the clinical landscape of diabetes mellitus (DM) therapy through their favourable effects on cardiovascular outcomes. Notably, the use of SGLT2i has been linked to cardiovascular benefits regardless of DM status, while their pleiotropic actions remain to be fully elucidated. What we do know is that SGLT2i exert beneficial effects even at the level of the myocardial cell and that these are linked to an improvement in the energy substrate, resulting in less inflammation and fibrosis. SGLT2i ameliorates myocardial extracellular matrix remodeling, cardiomyocyte stiffness and concentric hypertrophy, achieving beneficial remodeling of the left ventricle with significant implications for the pathogenesis and outcome of heart failure. Most studies show a significant improvement in markers of diastolic dysfunction along with a reduction in left ventricular hypertrophy. In addition to these effects, there is electrophysiological remodeling, which explains initial data suggesting that SGLT2i have an antiarrhythmic action against both atrial and ventricular arrhythmias. However, future studies need to clarify not only the exact mechanisms of this beneficial functional, structural, and electrophysiological cardiac remodeling but also its magnitude to determine whether this is a class or a drug effect.
钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）通过对心血管结局的有利影响改变了糖尿病（DM）治疗的临床格局。值得注意的是，无论 DM 状态如何，SGLT2i 的使用都与心血管获益有关，而其多效作用仍有待充分阐明。我们所知道的是，SGLT2i 甚至在心肌细胞水平上也能发挥有益的作用，这与改善能量底物有关，从而减少炎症和纤维化。SGLT2i 改善心肌细胞外基质重塑、心肌细胞僵硬和向心性肥大，实现左心室的有益重塑，对心力衰竭的发病机制和结局有重要意义。大多数研究表明，舒张功能障碍标志物显著改善，左心室肥厚减少。除了这些作用外，还有电生理重塑，这解释了最初的数据表明 SGLT2i 对房性和室性心律失常都有抗心律失常作用。然而，未来的研究不仅需要阐明这种有益的功能、结构和电生理心脏重塑的确切机制，还需要确定其程度，以确定这是一种类效应还是药物效应。
