Purpose Of Review: SGLT2 inhibitors (SGLT2i) are new drugs for patients with heart failure (HF) irrespective of diabetes. However, the mechanisms of SGLT2i in HF remain elusive. This article discusses the current clinical evidence for using SGLT2i in different types of heart failure and provides an overview about the possible underlying mechanisms.
Recent Findings: Clinical and basic data strongly support and extend the use of SGLT2i in HF. Improvement of conventional secondary risk factors is unlikely to explain the prognostic benefits of these drugs in HF. However, different multidirectional mechanisms of SGLT2i could improve HF status including volume regulation, cardiorenal mechanisms, metabolic effects, improved cardiac remodelling, direct effects on cardiac contractility and ion-homeostasis, reduction of inflammation and oxidative stress as well as an impact on autophagy and adipokines. Further translational studies are needed to determine the mechanisms of SGLT2i in HF. However, basic and clinical evidence encourage the use of SGLT2i in HFrEF and possibly HFpEF.
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http://dx.doi.org/10.1007/s11897-021-00529-8 | DOI Listing |
Ren Fail
December 2025
Department of Endocrinology, East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Background: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Sodium-glucose cotransporter protein 2 inhibitors (SGLT2i) are antihyperglycemic agents that provide additional renal-protective effects in patients with DKD, independent of their glucose-lowering effects. However, the underlying mechanism remains unclear.
View Article and Find Full Text PDFCardiovasc Res
December 2024
Translational Cardiovascular Medicine UR 3074, FMTS, 1 rue Eugène Boeckel, Strasbourg 67084, France.
Aims: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) show a cardioprotective effect in heart failure and myocardial infarction, pathologies often associated with low-grade inflammation. This cross-sectional study aims to investigate whether low-grade inflammation regulates SGLT2 expression and function in human vasculature, heart, and endothelial cells (ECs).
Methods And Results: Human internal thoracic artery (ITA), left ventricle (LV) specimens, and cultured porcine coronary artery ECs were used.
Expert Opin Drug Saf
December 2024
Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
Introduction: The risk of HCC is twice as high in diabetic patients compared to non-diabetic ones, suggesting that diabetes advances carcinogenesis in the liver through a variety of mechanisms. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to improve liver outcomes, emerging as promising agents to treat hepatocellular carcinoma (HCC) in patients with type 2 diabetes mellitus (T2DM).
Methods: We searched PubMed and Scopus databases for articles presenting an association between SGLT2is and HCC to explore the putative mechanisms of action underlying the anti-proliferative activity of SGLT2is.
J Clin Invest
December 2024
Division of Nutritional Science and Obesity Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Despite the impressive clinical benefits and widespread adoption of sodium glucose cotransporter 2 inhibitors (SGLT2i) to treat all classes of heart failure, their cardiovascular mechanisms of action are poorly understood. Proposed mechanisms range broadly and include enhanced ketogenesis, where the mild ketosis associated with SGLT2i use is presumed to be beneficial. However, in this issue of the JCI, carefully conducted metabolic flux studies by Goedeke et al.
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