The metabolic impact of these agents are associated with the elevation of ketone body production, activation of anti-inflammatory and antioxidative pathways, and reduction of advanced glycation end-products mediated effects [24, 25] Therefore, the mechanism of action of the SGLT2 inhibitors is complex and multifactorial [12, 25]. While these findings justify the administration of SGLT2 inhibitors for patients with HFrEF and diabetes, recent trials reported comparable benefits in nondiabetic HF patients [10]. The gene discussed is SLC5A2; the disease is diabetes mellitus.