Based on the recent cardiovascular outcome trials proposing that SGLT-2 inhibitors might be crucial for the treatment of special patient sub-populations, such as those with concomitant HF with reduced or preserved ejection fraction [21,22,23] or CKD [20], regardless of baseline T2DM, it seems that there is increasing interest in the underlying mechanisms mediating those beneficial effects. The gene discussed is SLC5A2; the disease is type 2 diabetes mellitus.