A DAPA-HF trial showed that patients with HF and reduced ejection fraction, irrespective of their Type 2 Diabetes Mellitus (T2DM) status, had less hospitalization due to acute decompensated HF and death from cardiovascular events, which suggests an unexplored mechanism of action of SGLT2-i other than glycosuria and diuresis [1]. This evidence concerns the gene SLC5A2 and hydrops fetalis.