Diabetes mellitus (DM) is the leading cause of end stage renal disease; 40% of the patients worldwide will require replacement therapy after 20 years of DM. Early-stage diabetic nephropathy is characterized by hyper filtration with micro-and macro albuminuria. Later on end-stage renal disease (ESRD) can appear; 40% of diabetic patients develop micro-and macrovascular complications, with increased risk among patients with genetic predisposition, such as Haptoglobin 2-2 phenotype. The most frequent complications are diabetic kidney disease, diabetic retinopathy and coronary artery disease. Chronic systemic inflammation and the inflammatory response, such as increased circulating cytokines have been recognized as main players in the development and progression of diabetic nephropathy. DM is also associated with increased oxidative stress, and alterations in carbohydrate, lipid and protein metabolism. Blocking the renin- angiotensin- aldosterone system (RAAS) is not sufficient to delay the progression of DM. Autophagy may be involved in the pathogenesis of diabetic nephropathy. Under normal blood glucose level, autophagy is an important protective mechanism in renal epithelial cells, including podocytes, proximal tubular, mesangial and endothelial cells. Down regulation of the autophagy mechanism, as in hyperglycemic condition, can contribute to the development and progression of DM. The recently used new family of drugs SGL2Tis (sodium-glucose cotransporter-2 inhibitors) reduces the typical glomerular hyper-filtration. Preclinical and clinical studies focusing on SGLT2I treatment have consistently demonstrated a reduction in albuminuria and maintenance of renal function. SGLT2 inhibition may lead to positive molecular changes in podocyte cells and proximal tubule cells by directly affect basal autophagy.