It was also speculated that SGLT-2 inhibitors may improve renal oxygen consumption, based on their pathophysiologic mechanisms of action and that such an effect may be beneficial both in the acute and the chronic HF setting [78]; however, the only available human trial to date failed to show any significant benefit with SGLT-2 inhibitor treatment on renal oxygen consumption in subjects without underlying diabetes and hypertension [79]. This evidence concerns the gene SLC5A2 and diabetes mellitus.