Rastogi Anjay, Januzzi James L
David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Massachusetts General Hospital, Boston, MA 02114, USA.
J Clin Med. 2023 Apr 12;12(8):2824. doi: 10.3390/jcm12082824.
Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to improve cardiovascular and renal outcomes in patients with established cardiovascular disease, chronic kidney disease (CKD), and heart failure (HF) with reduced or preserved ejection fraction. Clinical benefit has been substantiated in patients with and without type 2 diabetes (T2D). Consequently, SGLT2is have an increasingly important role in HF and CKD management that extends beyond T2D treatment. Their pleiotropic pharmacological effects underlying their cardiovascular and renal benefits are not completely understood but include significant effects beyond blood glucose reduction. SGLT2is inhibit the reabsorption of glucose and sodium in the proximal tubule which, in addition to lowering blood glucose, activates tubuloglomerular feedback, leading to reduced glomerular hydrostatic pressure and the mitigation of glomerular filtration rate loss. SGLT2is have diuretic and natriuretic effects, leading to decreased blood pressure, preload, and left ventricular (LV) filling pressure, and improvements in other surrogates of afterload. In HF, SGLT2is mitigate the risks of hyperkalemia and ventricular arrhythmia and improve LV dysfunction. SGLT2is also reduce sympathetic tone and uric acid levels, increase hemoglobin levels, and are postulated to have anti-inflammatory properties. This narrative review discusses the multifactorial and interrelated pharmacological mechanisms underlying the cardiovascular and renal benefits of SGLT2is.
钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）已被证明可改善已确诊心血管疾病、慢性肾脏病（CKD）以及射血分数降低或保留的心力衰竭（HF）患者的心血管和肾脏结局。无论有无2型糖尿病（T2D），临床获益均已得到证实。因此，SGLT2i在HF和CKD管理中的作用日益重要，其作用范围已超越T2D治疗。其心血管和肾脏获益背后的多效药理作用尚未完全明确，但包括除降低血糖之外的显著作用。SGLT2i抑制近端小管对葡萄糖和钠的重吸收，这除了降低血糖外，还激活管球反馈，导致肾小球静水压降低，减轻肾小球滤过率损失。SGLT2i具有利尿和排钠作用，可降低血压、前负荷和左心室（LV）充盈压，并改善其他后负荷替代指标。在HF中，SGLT2i可降低高钾血症和室性心律失常风险，并改善LV功能障碍。SGLT2i还可降低交感神经张力和尿酸水平，提高血红蛋白水平，并推测具有抗炎特性。本叙述性综述讨论了SGLT2i心血管和肾脏获益背后的多因素且相互关联的药理机制。
