2nd Department of Nephrology, AHEPA Hospital, Aristotle University of Thessaloniki, GR54636 Thessaloniki, Greece.
Department of Nephrology, School of Medicine, University of Thessaly, GR41110 Larissa, Greece.
Int J Mol Sci. 2023 Feb 1;24(3):2803. doi: 10.3390/ijms24032803.
Although sodium glucose co-transporter type 2 (SGLT-2) inhibitors were initially introduced as glucose-lowering medications, it was later discovered that cardiorenal protection is the most important treatment effect of these agents. A triad of landmark trials consistently showed the benefits of SGLT-2 inhibitors on kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD), irrespective of the presence or absence of Type 2 diabetes (T2D). Furthermore, finerenone is a novel, selective, nonsteroidal mineralocorticoid receptor antagonist (MRA) that safely and effectively improved cardiorenal outcomes in a large Phase 3 clinical trial program that included >13,000 patients with T2D and a wide spectrum of CKD. These two drug categories have shared and distinct mechanisms of action, generating the hypothesis that an overadditive cardiorenal benefit with their combined use may be biologically plausible. In this article, we describe the mechanism of action, and we provide an overview of the evidence for cardiorenal protection with SGLT-2 inhibitors and the nonsteroidal MRA finerenone in patients with CKD associated with T2D.
尽管钠-葡萄糖共转运蛋白 2（SGLT-2）抑制剂最初被引入作为降血糖药物，但后来发现，心脏和肾脏保护是这些药物最重要的治疗效果。三项具有里程碑意义的试验一致表明，SGLT-2 抑制剂可改善慢性肾脏病（CKD）患者的肾脏和心血管结局，无论是否存在 2 型糖尿病（T2D）。此外，非奈利酮是一种新型、选择性、非甾体类盐皮质激素受体拮抗剂（MRA），在一项包括超过 13000 例 T2D 和广泛 CKD 患者的大型 3 期临床试验项目中，安全有效地改善了心脏和肾脏结局。这两类药物具有共同和独特的作用机制，产生了一个假设，即它们联合使用可能具有生物学上的合理性，从而产生额外的心脏和肾脏益处。在本文中，我们描述了 SGLT-2 抑制剂和非甾体 MRA 非奈利酮的作用机制，并概述了它们在伴有 T2D 的 CKD 患者中的心脏和肾脏保护作用的证据。
