Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
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.

PubMed Disclaimer

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

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Salvatore T., Carbonara O., Cozzolino D., Torella R., Nasti R., Lascar N., Sasso F.C. Kidney in diabetes: From organ damage _target to therapeutic _target. Curr. Drug Metab. 2011;12:658–666. doi: 10.2174/138920011796504509. - DOI - PubMed
    1. DeFronzo R.A., Hompesch M., Kasichayanula S., Liu X., Hong Y., Pfister M., Morrow L.A., Leslie B.R., Boulton D.W., Ching A., et al. Characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 diabetes. Diabetes Care. 2013;36:3169–3176. doi: 10.2337/dc13-0387. - DOI - PMC - PubMed
    1. Merovci A., Mari A., Solis-Herrera C., Xiong J., Daniele G., Chavez-Velazquez A., Tripathy D., Urban McCarthy S., Abdul-Ghani M., DeFronzo R.A. Dapagliflozin lowers plasma glucose concentration and improves β-cell function. J. Clin. Endocrinol. Metab. 2015;100:1927–1932. doi: 10.1210/jc.2014-3472. Erratum in J. Clin. Endocrinol. Metab. 2017, 102, 4662. - DOI - PMC - PubMed
    1. De Konink L. Observations sur les proprietes febrifuges de la phloridzine. Bull. Soc. Med. Gand. 1836;1:75–110.
    1. Chasis H., Jolliffe N., Smith H.W. The action of phlorizin on the excretion of glucose, xylose, sucrose, creatinine and urea by man. J. Clin. Investig. 1933;12:1083–1090. doi: 10.1172/JCI100559. - DOI - PMC - PubMed

MeSH terms

Substances

  NODES
twitter 2