Notably, the first large phase-3 trial of SGLT2 inhibitors enrolling patients without diabetes was the DAPA-HF trial, which showed that, in patients with heart failure and reduced ejection fraction, those receiving dapagliflozin had a lower risk of worsening heart failure or death from cardiovascular causes, regardless of the presence of diabetes (McMurray et al., 2019). This evidence concerns the gene SLC5A2 and hydrops fetalis.