A Review of the Mechanism of Cardiac Benefit of Sodium-Glucose Cotransporter 2 Inhibitors
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Keywords

SGLT2i
Circulatory load
Cardiomyocyte
Myocardial energy

DOI

10.26689/jcnr.v6i2.3559

Submitted : 2023-06-06
Accepted : 2023-06-21
Published : 2023-07-06

Abstract

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a new type of hypoglycemic drug, which can reduce the excitability of sympathetic nerve by regulating the metabolism of energy substrate, electrolyte, tissue fluid and circulating blood volume in the ganglion, interfering with inflammation and oxidative stress, offering protection to vascular endothelial cells, maintaining vasodilation function, regulating volume and pressure load and myocardial energy metabolism, as well as protecting cardiomyocytes and cardiac function.

References

Docherty KF, Jhund PS, Claggett B, et al., 2021, Extrapolating Long-term Event-Free and Overall Survival

with Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction: An Exploratory Analysis

of a Phase 3 Randomized Clinical Trial. JAMA Cardiol, 6(11): 1298–1305.

Beitelshees AL, Leslie BR, Taylor SI, 2019, Sodium-Glucose Cotransporter 2 Inhibitors: A Case Study in

Translational Research. Diabetes, 68(6): 1109–1120.

Packer M, Anker SD, Butler J, et al., 2021, Empagliflozin in Patients with Heart Failure, Reduced Ejection

Fraction, and Volume Overload: EMPEROR-Reduced Trial. J Am Coll Cardiol, 77(11): 1381–1392.

Liu B, Wang Y, Zhang Y, et al., 2019, Mechanisms of Protective Effects of SGLT2 Inhibitors in

Cardiovascular Disease and Renal Dysfunction. Curr Top Med Chem, 19(20): 1818–1849.

Scheen AJ. 2019, Effect of SGLT2 Inhibitors on the Sympathetic Nervous System and Blood Pressure.

Curr Cardiol Rep, 21(8): 70.

Gray CB, Suetomi T, Xiang S, et al., 2017, CaMKII Delta Subtypes Differentially Regulate Infarct

Formation Following Ex Vivo Myocardial Ischemia/Reperfusion Through NF-kappaB and TNF-alpha. J

Mol Cell Cardiol, 103: 48–55.

Zelniker TA, Braunwald E, 2020, Mechanisms of Cardiorenal Effects of Sodium-Glucose Cotransporter 2

Inhibitors: JACC State-of-the-Art Review. J Am Coll Cardiol, 75(4): 422–434.

Sayour AA, Celeng C, Olah A, et al., 2021, Sodium-Glucose Cotransporter 2 Inhibitors Reduce Myocardial

Infarct Size in Preclinical Animal Models of Myocardial Ischaemia-Reperfusion Injury: A Meta-Analysis.

Diabetologia, 64(4): 737–748.

Wang K, Li Z, Sun Y, et al., 2021, Dapagliflozin Improves Cardiac Function, Remodeling, Myocardial

Apoptosis, and Inflammatory Cytokines in Mice with Myocardial Infarction. J Cardiovasc Transl Res.

http://doi.org/10.1007/s12265-021-10192-y

Li X, Lu Q, Qiu Y, et al., 2021, Direct Cardiac Actions of the Sodium Glucose Co-Transporter 2 Inhibitor

Empagliflozin Improve Myocardial Oxidative Phosphorylation and Attenuate Pressure-Overload Heart

Failure. J Am Heart Assoc, 10(6): e18298.

Lopaschuk GD, Karwi QG, Tian R, et al., 2021, Cardiac Energy Metabolism in Heart Failure. Circulation

Research, 128(10): 1487–1513.

Verma S, Rawat S, Ho KL, et al., 2018, Empagliflozin Increases Cardiac Energy Production in Diabetes:

Novel Translational Insights into the Heart Failure Benefits of SGLT2 Inhibitors. JACC Basic Transl Sci,

(5): 575–587.

Yurista SR, Nguyen CT, Rosenzweig A, et al., 2021, Ketone Bodies for the Failing Heart: Fuels that can

Fix the Engine? Trends Endocrinol Metab, 32(10): 814–826.

Kanbay M, Tapoi L, Ureche C, et al., 2021, Effect of Sodium-Glucose Cotransporter 2 Inhibitors on

Hemoglobin and Hematocrit Levels in Type 2 Diabetes: A Systematic Review and Meta-Analysis. Int Urol

Nephrol. http://doi.org/10.1007/s11255-021-02943-2