The tremendous cardiac benefits of SGLT2 inhibitors emerged for the first time from the major cardiovascular safety trials of these drugs, such as DECLARE-TIMI 58 and EMPA-REG OUTCOME, which showed that SGLT2 inhibitors therapy was associated with remarkable improvements in cardiovascular outcomes, including a reduction in mortality and HF hospitalization [104,105]. This evidence concerns the gene SLC5A2 and hydrops fetalis.