Among the cardioprotective effects, SGLT2-Is determine preload and afterload reduction, with improved hemodynamics; adipose tissue, body weight, and insulin resistance decrease, with reduced oxidative stress and endothelial inflammation; ketogenesis increase, with improved mitochondrial function and cardiomyocyte energy efficiency; and Na+/H+ exchanger activity inhibition, with reduced intracellular Na+ concentration and arrhythmias, myocardial hypertrophy, and HF progression incidence. The gene discussed is SLC5A2; the disease is Insulin resistance.