Nikolic Maja, Zivkovic Vladimir, Jovic Jovana Joksimovic, Sretenovic Jasmina, Davidovic Goran, Simovic Stefan, Djokovic Danijela, Muric Nemanja, Bolevich Sergey, Jakovljevic Vladimir
Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
Heart Fail Rev. 2022 May;27(3):935-949. doi: 10.1007/s10741-021-10079-9. Epub 2021 Feb 3.
This paper highlights the cardioprotective potential of sodium-glucose cotransporter 2 inhibitors (SLGT2i), as well as several most discussed mechanisms responsible for their cardioprotection. Cardiovascular diseases are considered a primary cause of death in nearly 80% of type 2 diabetes mellitus (T2DM) patients, with a 2-4-fold greater incidence of heart failure (HF) among diabetics. As novel hypoglycemics, SGLT2i showed exceptional cardiovascular benefits, reflected through robust reductions of cardiovascular mortality and hospitalization for HF in T2DM patients. Recently, those effects have been reported even in patients with HF and reduced ejection fraction irrespectively of diabetic status, suggesting that cardioprotective effects of SGLT2i are driven independently of their hypoglycemic actions. SGLT2i exerted hemodynamic and metabolic effects, partially driven by natriuresis and osmotic diuresis. However, those systemic effects are modest, and therefore cannot be completely related to the cardiac benefits of these agents in T2DM patients. Hence, increased circulating ketone levels during SGLT2i administration have brought out another hypothesis of a cardiac metabolic switch. Moreover, SGLT2i influence ion homeostasis and exert anti-inflammatory and antifibrotic effects. Their enviable influence on oxidative stress markers, as well as anti- and pro-apoptotic factors, have also been reported. However, since the main mechanistical contributor of their cardioprotection has not been elucidated yet, a joint action of systemic and molecular mechanisms has been suggested. In the light of ongoing trials evaluating the effects of SGLT2i in patients with HF and preserved ejection fraction, a new chapter of beneficial SGLT2i mechanisms is expected, which might resolve their main underlying action.
本文强调了钠-葡萄糖协同转运蛋白2抑制剂（SLGT2i）的心脏保护潜力，以及几种讨论最多的介导其心脏保护作用的机制。心血管疾病被认为是近80%的2型糖尿病（T2DM）患者的主要死因，糖尿病患者发生心力衰竭（HF）的几率要高2至4倍。作为新型降糖药，SGLT2i显示出卓越的心血管益处，表现为T2DM患者心血管死亡率和因HF住院率大幅降低。最近，即使在射血分数降低的HF患者中也报道了这些作用，且与糖尿病状态无关，这表明SGLT2i的心脏保护作用独立于其降糖作用。SGLT2i发挥血液动力学和代谢作用，部分由利钠和渗透性利尿驱动。然而，这些全身作用较小，因此不能完全解释这些药物对T2DM患者心脏的益处。因此，SGLT2i给药期间循环酮水平升高引出了心脏代谢转换的另一种假说。此外，SGLT2i影响离子稳态并发挥抗炎和抗纤维化作用。也有报道称它们对氧化应激标志物以及抗凋亡和促凋亡因子有令人羡慕的影响。然而，由于其心脏保护作用的主要机制尚未阐明，有人提出全身机制和分子机制共同起作用。鉴于正在进行评估SGLT2i对射血分数保留的HF患者影响的试验，预计将开启有益的SGLT2i机制的新篇章，这可能会揭示其主要潜在作用。
