Abstract: Chronic kidney disease (CKD) is the most common complication of patients with type 2 diabetes (T2DM) and is an independent risk factor for cardiovascular disease. Most oral glucoselowering drugs and their metabolites are excreted via kidneys; extension of the halflife, drug accumulation induced hypoglycemia and other adverse reactions are seen in patients with renal impairment. The renal conditions of patients with T2DM and CKD should be considered when prescribing glucoselowering drugs; the drugs with clear renal benefits, low hypoglycemia risk and those are excreted via kidneys the least are preferred. Dipeptidyl peptidase4 inhibitor (DPP4i) has been commonly used in clinic due to its unique mechanism of action, glycemic control effect, low risk for hypoglycemia and weight gain, as well as simplicity to use. The four major cardiovascular outcome trials (CVOTs) also evaluated the efficacy and safety of DPP4is in patients with T2DM and different renal conditions. Although the glycemic control effects of the four DPP4is are similar, the characteristic of each DPP4i differs from each other, as well as the cardiovascular and renal outcomes in patients treated with different DPP4is also differ. This review aimed to summarize and compare the data regarding cardiovascular and renal outcomes in patients with T2DM and different renal conditions who received DPP4i in the CVOTs; as well as to discuss the mechanisms of action underlying the renal benefits of DPP4i in order to provide evidence on the treatment of DPP4i in patients with T2DM and CKD.

Key words: type 2 diabetes, chronic kidney disease, kidney dysfunction, dipeptidyl peptidase-4 inhibitor, cardiovascular and renal safety