Lee Yong-Ho, Lim Soo, Davies Melanie J
Department of Internal Medicine, Institute for Innovation in Digital Healthcare (IIDH), Institute for Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Nat Rev Endocrinol. 2025 Sep 11. doi: 10.1038/s41574-025-01170-4.
The therapeutic scope of sodium-glucose cotransporter 2 (SGLT2) inhibitors has expanded beyond glycaemic regulation in the management of diabetes mellitus. Studies published in the past few years highlight their substantial effect on cardiovascular outcomes, notably in decreasing mortality and the need for heart failure-related hospitalization. These agents also lead to pronounced improvements in a range of renal outcomes. The primary actions of SGLT2 inhibition, glycosuria and natriuresis, are pivotal in enhancing glucose control, promoting weight loss and lowering blood pressure. These effects initiate a series of beneficial mechanisms: facilitating haemodynamic improvement by reducing interstitial volume, enhancing cardiac function, boosting energy efficiency through altered ketone body metabolism and mitigating inflammation and oxidative stress. Additional effects include heightened erythropoiesis, reduced hyperuricaemia and increased levels of angiotensin-converting enzyme 2 and angiotensin (1-7). SGLT2 inhibitors also attenuate sympathetic overactivity by modulating neurohumoral activation and renal afferent signalling, contributing to their cardioprotective and renoprotective profiles. This Review provides a comprehensive overview of the diverse mechanisms underpinning the cardiometabolic and renal effects of SGLT2 inhibitors, emphasizing their clinical relevance and therapeutic potential.
在糖尿病管理中，钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂的治疗范围已超出血糖调节。过去几年发表的研究突出了它们对心血管结局的显著影响，尤其是在降低死亡率和减少心力衰竭相关住院需求方面。这些药物还能显著改善一系列肾脏结局。SGLT2抑制的主要作用，即糖尿和利钠作用，对于加强血糖控制、促进体重减轻和降低血压至关重要。这些作用引发了一系列有益机制：通过减少间质容量促进血流动力学改善、增强心脏功能、通过改变酮体代谢提高能量效率以及减轻炎症和氧化应激。其他作用包括增强红细胞生成、降低高尿酸血症以及提高血管紧张素转换酶2和血管紧张素（1-7）水平。SGLT2抑制剂还通过调节神经体液激活和肾传入信号来减轻交感神经过度活动，这有助于其心脏保护和肾脏保护作用。本综述全面概述了SGLT2抑制剂对心脏代谢和肾脏作用的多种机制，强调了它们的临床相关性和治疗潜力。
