Rolski Filip, Mączewski Michał
Department of Clinical Physiology, Centre of Postgraduate Medical Education, 99/103 Marymoncka Str., 01-813 Warsaw, Poland.
Pharmaceuticals (Basel). 2025 Feb 24;18(3):313. doi: 10.3390/ph18030313.
Sodium-glucose cotransporter 2 inhibitors (SGLT2is), commonly known as flozins, have garnered attention not only for their glucose-lowering effects in type 2 diabetes mellitus (T2DM) but also for their cardioprotective properties. This review examines the mechanisms underlying the anti-fibrotic effects of SGLT2is, with a focus on key clinical trials and preclinical models. SGLT2is, mainly empagliflozin and dapagliflozin, have demonstrated significant reductions in heart failure-related hospitalizations, cardiovascular death, and fibrosis markers, independent of their glucose-lowering effects. The cardioprotective benefits appear to stem from direct actions on cardiac tissues, modulation of inflammatory responses, and improvements in metabolic parameters. In animal models of heart failure, SGLT2is were demonstrated to reduce cardiac fibrosis through mechanisms involving AMPK activation, reduced oxidative stress, and inhibition of pro-fibrotic pathways, not only through the inhibition of SGLT2 present on cardiac cells but also by targeting several other molecular targets. These findings confirm their efficacy in the treatment of heart failure and align with evidence from human trials, supporting the potential involvement of multiple pathways in mediating cardiac fibrosis. These results also provide a promising basis for clinical trials specifically targeting pathways shared with SGLT2is.
钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i），通常被称为“列净类药物”，不仅因其在2型糖尿病（T2DM）中的降糖作用而受到关注，还因其心脏保护特性而备受瞩目。本综述探讨了SGLT2i抗纤维化作用的潜在机制，重点关注关键临床试验和临床前模型。SGLT2i，主要是恩格列净和达格列净，已证明可显著降低与心力衰竭相关的住院率、心血管死亡率和纤维化标志物，且与其降糖作用无关。心脏保护益处似乎源于对心脏组织的直接作用、炎症反应的调节以及代谢参数的改善。在心力衰竭动物模型中，SGLT2i被证明可通过涉及AMPK激活、降低氧化应激和抑制促纤维化途径的机制减少心脏纤维化，这不仅是通过抑制心脏细胞上存在的SGLT2，还通过靶向其他几个分子靶点。这些发现证实了它们在治疗心力衰竭方面的疗效，并与人体试验的证据一致，支持多种途径可能参与介导心脏纤维化。这些结果也为专门针对与SGLT2i共享途径的临床试验提供了有前景的基础。
