Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Chiba 272-8516, Japan.
Int J Mol Sci. 2021 Apr 23;22(9):4416. doi: 10.3390/ijms22094416.
Sodium glucose cotransporter 2 inhibitors (SGLT2i) block the reabsorption of glucose by inhibiting SGLT2, thus improving glucose control by promoting the renal excretion of glucose, without requiring insulin secretion. This pharmacological property of SGLT2i reduces body weight and improves insulin resistance in diabetic patients. Such beneficial metabolic changes caused by SGLT2i are expected to be useful not only for glucose metabolism, but also for the protection for various organs. Recent randomized controlled trials (RCTs) on cardiovascular diseases (EMPA-REG OUTCOME trial and CANVAS program) showed that SGLT2i prevented cardiovascular death and the development of heart failure. RCTs on renal events (EMPA-REG OUTCOME trial, CANVAS program, and CREDENCE trial) showed that SGLT2i suppressed the progression of kidney disease. Furthermore, SGLT2i effectively lowered the liver fat content, and our study demonstrated that SGLT2i reduced the degree of hepatic fibrosis in patients at high-risk of hepatic fibrosis. Such promising properties of SGLT2i for cardiovascular, renal, and hepatic protection provide us the chance to think about the underlying mechanisms for SGLT2i-induced improvement of multiple organs. SGLT2i have various mechanisms for organ protection beyond glucose-lowering effects, such as an increase in fatty acids utilization for hepatic protection, osmotic diuresis for cardiac protection, an improvement of insulin resistance for anti-atherogenesis, and an improvement of tubuloglomerular feedback for renal protection.
钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）通过抑制 SGLT2 来阻止葡萄糖的重吸收，从而通过促进肾脏排糖来改善血糖控制，而无需胰岛素分泌。SGLT2i 的这种药理学特性可降低糖尿病患者的体重并改善胰岛素抵抗。SGLT2i 引起的这种有益的代谢变化不仅有望对葡萄糖代谢有用，而且对各种器官的保护也有用。最近关于心血管疾病的随机对照试验（EMPA-REG OUTCOME 试验和 CANVAS 项目）表明，SGLT2i 可预防心血管死亡和心力衰竭的发生。关于肾脏事件的 RCT（EMPA-REG OUTCOME 试验、CANVAS 项目和 CREDENCE 试验）表明，SGLT2i 可抑制肾脏疾病的进展。此外，SGLT2i 可有效降低肝脂肪含量，我们的研究表明，SGLT2i 可降低高危肝纤维化患者的肝纤维化程度。SGLT2i 在心血管、肾脏和肝脏保护方面的这些有前途的特性使我们有机会思考 SGLT2i 改善多个器官的潜在机制。SGLT2i 除了具有降低血糖的作用外，还有许多针对器官保护的机制，例如增加脂肪酸的利用以保护肝脏、通过渗透利尿保护心脏、改善胰岛素抵抗以抗动脉粥样硬化形成、以及改善管球反馈以保护肾脏。
