Potential mechanisms of cardiac protection with SGLT2i include renin-angiotensin system inhibition following decreased total body sodium content, reduced myocardial cytoplasmic sodium and calcium load, anti-apoptotic, anti-inflammatory, anti-oxidant effects, rescue of diabetes myocardial microvascular injuries, and reduced sympathetic overactivity, inactivation of endoplasmic reticulum stress [6, 12, 38–42]. This evidence concerns the gene REN and diabetes mellitus.