Sodium-glucose co-transporter 2 inhibitor therapy: mechanisms of action in heart failure
Top Cited Papers
Open Access
- 26 February 2021
- Vol. 107 (13), 1032-1038
- https://doi.org/10.1136/heartjnl-2020-318060
Abstract
Patients with type 2 diabetes mellitus are at a higher risk of developing heart failure compared with the healthy population. In recent landmark clinical trials, sodium-glucose co-transporter 2 (SGLT2) inhibitor therapies improve blood glucose control and also reduce cardiovascular events and heart failure hospitalisations in patients with type 2 diabetes. Intriguingly, such clinical benefits have also been seen in patients with heart failure in the absence of type 2 diabetes although the underlying mechanisms are not clearly understood. Potential pathways include improved glycaemic control, diuresis, weight reduction and reduction in blood pressure, but none fully explain the observed improvements in clinical outcomes. More recently, novel mechanisms have been proposed to explain these benefits that include improved cardiomyocyte calcium handling, enhanced myocardial energetics, induced autophagy and reduced epicardial fat. We provide an up-to-date review of cardiac-specific SGLT2 inhibitor–mediated mechanisms and highlight studies currently underway investigating some of the proposed mechanisms of action in cardiovascular health and disease.Keywords
Funding Information
- AstraZeneca (SJ is also supported by an investigator initiated)
- Medical Research Council (TS is supported by MRC CRTF (MR/T029153/1))
- Wellcome Trust (DEN is the recipient of a Wellcome Trust Senior In)
- British Heart Foundation (DEN is supported by the BHF (CH/09/002, RG/16/10/3, SJ is supported by a BHF REA fellowship (RE/18/5/3)
- British Heart Foundation, Medical Research Council, Wellcome Trust, AstraZeneca (The authors are supported by British Heart Foundation [SJ, RE/18/5/3 and FS/CRTF/20/24087; TS, RE/18/5/3; DEN, CH/09/002, RG/18/5/3), Medical Research Council (TS, MR/T029153/1), Wellcome Trust (DEN, WT103782AIA) and an investigator initiated award from AstraZeneca (SJ, SER-19-20118)])
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