A large amount of recent epidemiological studies have shown the worldwide growth on the incidence and prevalence of diabetes mellitus type II (DM2), especially in industrialized countries where DM2 is the most frequent cause of chronic kidney disease. Diabetic nephropathy progression to ESRD (End Stage Renal Disease) may be slowed down only with a tight glycemic control, since no hypoglycemic drugs have been shown to possess renoprotective effects. Treatment with oral hypoglycemic agents should be closely and regularly monitored in patients with diabetic nephropathy since the decline of renal function below 60 ml/min of glomerular filtration rate (GFR) could cause multiple pharmacokinetic alterations. It may expose the patient to serious side effects if cautious dose reduction or even withdrawal of these drugs is not considered. Pharmacological approaches to the treatment of diabetes type 2 include the traditional oral hypoglycemic drugs (insulin sensitizers, insulin secretagogues and drugs inhibiting the absorption of glucose), incretin system drugs (orally or intravenously administered) and insulin therapy, if these drugs are insufficient or are contraindicated. The objective of this review is to evaluate the evidence regarding the use of oral hypoglycemic agents (with particular attention to the DPP-4 inhibitors) in diabetes type 2 with chronic kidney disease stage III- IV and ESRD, while in case of eGFR > 60 ml / min no dosage adjustment is usually required.