Diabetes mellitus (DM) is the most important cause of end-stage renal disease, blindness, autonomic neuropathy, and heart failure. These complications endanger life expectancy, quality of life, and health costs in patients suffering from DM. These complications start to develop, especially in type 2 DM (T2DM), before the onset of this disease. Accumulating evidence proves that complications of diabetes are due to hyperglycemia that develops many years before the patients fulfill the diagnostic criteria of T2DM. Pathologic changes of diabetic kidney disease (DKD) in these patients have already developed by the time of onset of frank DM but are still clinically silent. These facts can explain the failure of the different sodium–glucose cotransporter 2 inhibitors (SGLT2Is) to completely prevent renal events even in diabetic patients with apparently normal kidneys. Many studies have used different SGLT2Is in patients devoid of diabetes without the fear of hypoglycemia. Available evidence pushes toward the use of SGLT2Is as early as the onset of prediabetes. This approach would eradicate not only DKD but also other known complications. The use of these agents by the onset of T1DM might be also justifiable. The early use of SGLT2Is as early as the onset of prediabetes might abort the development of DKD completely. This review provides insights for prospective studies that would make this hope a reality.