With an increasing number of trials reporting on SGLT2 inhibitors in patients with and without diabetes, the goal of this systematic review and meta-analysis is to provide a concise evaluation of all the available evidence so far and analyse the data from the existing studies that focus on patients with heart failure, so as to better comprehend the clinical implications of the use of SGLT2 inhibitors. This evidence concerns the gene SLC5A2 and diabetes mellitus.