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Review
. 2022 Mar 26;23(7):3651.
doi: 10.3390/ijms23073651.

An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors

Teresa Salvatore  1 , Raffaele Galiero  2 , Alfredo Caturano  2 , Luca Rinaldi  2 , Anna Di Martino  2 , Gaetana Albanese  2 , Jessica Di Salvo  2 , Raffaella Epifani  2 , Raffaele Marfella  2   3 , Giovanni Docimo  2 , Miriam Lettieri  4 , Celestino Sardu  2 , Ferdinando Carlo Sasso  2
Affiliations
Review

An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors

Teresa Salvatore et al. Int J Mol Sci. .

Abstract

Sodium-glucose co-transporter 2 (SGLT2) inhibitors block glucose reabsorption in the renal proximal tubule, an insulin-independent mechanism that plays a critical role in glycemic regulation in diabetes. In addition to their glucose-lowering effects, SGLT2 inhibitors prevent both renal damage and the onset of chronic kidney disease and cardiovascular events, in particular heart failure with both reduced and preserved ejection fraction. These unexpected benefits prompted changes in treatment guidelines and scientific interest in the underlying mechanisms. Aside from the _target effects of SGLT2 inhibition, a wide spectrum of beneficial actions is described for the kidney and the heart, even though the cardiac tissue does not express SGLT2 channels. Correction of cardiorenal risk factors, metabolic adjustments ameliorating myocardial substrate utilization, and optimization of ventricular loading conditions through effects on diuresis, natriuresis, and vascular function appear to be the main underlying mechanisms for the observed cardiorenal protection. Additional clinical advantages associated with using SGLT2 inhibitors are antifibrotic effects due to correction of inflammation and oxidative stress, modulation of mitochondrial function, and autophagy. Much research is required to understand the numerous and complex pathways involved in SGLT2 inhibition. This review summarizes the current known mechanisms of SGLT2-mediated cardiorenal protection.

Keywords: cardiorenal protection; cardiorenal syndrome; cardiovascular disease; diabetic kidney disease; gliflozins; type 2 diabetes mellitus.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Summary of cardiorenal protective effects driven by inhibition of SGLT2.
Figure 2
Figure 2
Overview of the main pleiotropic effects of SGLT2-inhibitors on the heart.
Figure 3
Figure 3
Reabsorption of glucose and sodium in the renal proximal tubule.
See this image and copyright information in PMC

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