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Review

Impact of SGLT2 Inhibitors on Heart Failure: From Pathophysiology to Clinical Effects

1
Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, I-80131 Naples, Italy
2
Division of Cardiology, A.O.R.N. “Sant’Anna & San Sebastiano”, I-81100 Caserta, Italy
3
Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
4
Department of Precision Medicine, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Angela Sciacqua and Elena Succurro
Int. J. Mol. Sci. 2021, 22(11), 5863; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115863
Received: 22 April 2021 / Revised: 24 May 2021 / Accepted: 25 May 2021 / Published: 30 May 2021
Heart failure (HF) affects up to over 20% of patients with type 2 diabetes (T2DM), even more in the elderly. Although, in T2DM, both hyperglycemia and the proinflammatory status induced by insulin resistance are crucial in cardiac function impairment, SGLT2i cardioprotective mechanisms against HF are several. In particular, these beneficial effects seem attributable to the significant reduction of intracellular sodium levels, well-known to exert a cardioprotective role in the prevention of oxidative stress and consequent cardiomyocyte death. From a molecular perspective, patients’ exposure to gliflozins’ treatment mimics nutrient and oxygen deprivation, with consequent autophagy stimulation. This allows to maintain the cellular homeostasis through different degradative pathways. Thus, since their introduction in the clinical practice, the hypotheses on SGLT2i mechanisms of action have changed: from simple glycosuric drugs, with consequent glucose lowering, erythropoiesis enhancing and ketogenesis stimulating, to intracellular sodium-lowering molecules. This provides their consequent cardioprotective effect, which justifies its significant reduction in CV events, especially in populations at higher risk. Finally, the updated clinical evidence of SGLT2i benefits on HF was summarized. Thus, this review aimed to analyze the cardioprotective mechanisms of sodium glucose transporter 2 inhibitors (SGLT2i) in patients with HF, as well as their clinical impact on cardiovascular events. View Full-Text
Keywords: SGLT2 inhibitors; heart failure; pathophysiology; type 2 diabetes; cardiovascular risk SGLT2 inhibitors; heart failure; pathophysiology; type 2 diabetes; cardiovascular risk
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MDPI and ACS Style

Palmiero, G.; Cesaro, A.; Vetrano, E.; Pafundi, P.C.; Galiero, R.; Caturano, A.; Moscarella, E.; Gragnano, F.; Salvatore, T.; Rinaldi, L.; Calabrò, P.; Sasso, F.C. Impact of SGLT2 Inhibitors on Heart Failure: From Pathophysiology to Clinical Effects. Int. J. Mol. Sci. 2021, 22, 5863. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115863

AMA Style

Palmiero G, Cesaro A, Vetrano E, Pafundi PC, Galiero R, Caturano A, Moscarella E, Gragnano F, Salvatore T, Rinaldi L, Calabrò P, Sasso FC. Impact of SGLT2 Inhibitors on Heart Failure: From Pathophysiology to Clinical Effects. International Journal of Molecular Sciences. 2021; 22(11):5863. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115863

Chicago/Turabian Style

Palmiero, Giuseppe, Arturo Cesaro, Erica Vetrano, Pia C. Pafundi, Raffaele Galiero, Alfredo Caturano, Elisabetta Moscarella, Felice Gragnano, Teresa Salvatore, Luca Rinaldi, Paolo Calabrò, and Ferdinando C. Sasso 2021. "Impact of SGLT2 Inhibitors on Heart Failure: From Pathophysiology to Clinical Effects" International Journal of Molecular Sciences 22, no. 11: 5863. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115863

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