The Mitochondrial Protective Mechanisms Mediated by SGLT2i: From Molecular Basis to Clinical Implications.
1.
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel class of oral hypoglycemic agents that selectively inhibit glucose reabsorption in the renal proximal tubules, thereby promoting urinary glucose excretion and reducing blood glucose levels. In recent years, accumulating evidence from large-scale clinical trials has demonstrated that SGLT2i not only exert robust glucose-lowering effects but also confer significant protective benefits on the cardiovascular, renal, and nervous systems. However, the precise molecular mechanisms underlying these multi-system benefits remain incompletely understood.2.
Mitochondria are central organelles responsible for cellular energy metabolism, redox homeostasis, and calcium handling, and they play a pivotal role in the pathogenesis and progression of various chronic diseases.3.
Emerging studies indicate that SGLT2i can markedly improve mitochondrial function through multiple mechanisms, including enhancement of mitochondrial quality control, modulation of mitochondrial energy metabolism, reinforcement of antioxidant defenses, and improvement of calcium homeostasis.4.
These mitochondria-centered mechanisms may underlie the protective effects of SGLT2i on the cardiovascular, renal, and neurological systems. In this review, we systematically summarize the regulatory effects of SGLT2i on mitochondrial function and discuss their potential therapeutic implications in related diseases, aiming to provide novel insights and a theoretical foundation for future basic research and clinical applications.
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel class of oral hypoglycemic agents that selectively inhibit glucose reabsorption in the renal proximal tubules, thereby promoting urinary glucose excretion and reducing blood glucose levels. In recent years, accumulating evidence from large-scale clinical trials has demonstrated that SGLT2i not only exert robust glucose-lowering effects but also confer significant protective benefits on the cardiovascular, renal, and nervous systems. However, the precise molecular mechanisms underlying these multi-system benefits remain incompletely understood.2.
Mitochondria are central organelles responsible for cellular energy metabolism, redox homeostasis, and calcium handling, and they play a pivotal role in the pathogenesis and progression of various chronic diseases.3.
Emerging studies indicate that SGLT2i can markedly improve mitochondrial function through multiple mechanisms, including enhancement of mitochondrial quality control, modulation of mitochondrial energy metabolism, reinforcement of antioxidant defenses, and improvement of calcium homeostasis.4.
These mitochondria-centered mechanisms may underlie the protective effects of SGLT2i on the cardiovascular, renal, and neurological systems. In this review, we systematically summarize the regulatory effects of SGLT2i on mitochondrial function and discuss their potential therapeutic implications in related diseases, aiming to provide novel insights and a theoretical foundation for future basic research and clinical applications.