As experimental studies led to the hypothesis that SGLT2-is might improve myocardial perfusion, this concept was directly tested in the SIMPLE trial, which evaluated the impact of empagliflozin treatment versus placebo on myocardial flow reserve (MFR), directly quantitated by positron emission tomography/computed tomography (PET/CT) at rest and during adenosine stress, in patients with type 2 DM and ischemic heart disease or other cardiovascular risk factors. The gene discussed is SLC5A2; the disease is coronary artery disorder.