Type 2 diabetes mellitus, along with complications that accompany it, have become a major threatening life disease in the 21st century. Although the association between glycated hemoglobin (HbA1c) and macrovascular complications has been known for many years, antidiabetic drugs have not been able to reduce these problems. The 2019 European Association of Cardiology/European Association for the Study of Diabetes guidelines on diabetes, prediabetes and heart disease recommend sodium-glucose cotransporter 2 inhibitors (SGLT2i) over metformin as first-line therapy in patients with atherosclerotic cardiovascular disease (ASCVD) or high or very high risk. Unlike many other antihyperglycemic therapies, increasing glucose excretions via SGLT2 inhibition provides hypoglycemic effects independent of insulin. The use of SGLT2 inhibitors may have beneficial effects on biomarkers such as blood glucose, blood pressure, body weight, intrarenal hemodynamics and proteinuria, and may also reduce cardiovascular complications, kidney disease and diabetes. The American Diabetes Association now recommends the use of SGLT2 inhibitors after initial treatment with dietary and lifestyle changes in addition to metformin in patients with T2DM and all cardiovascular diseases, including heart failure. SGLT2 inhibitors will become an important tool in the hands of physicians in daily practice targeting this vulnerable population.