DPP-4 Inhibitors in Diabetic Patients with Chronic Kidney Disease and End-Stage Kidney Disease on Dialysis in Clinical Practice

Abstract

Numerous drugs with different mechanisms of action and different pharmacologic profiles are being used with the aim of improving glycemic control in patients with type 2 diabetes. The therapeutic options for patients with type 2 diabetes and chronic kidney disease (CKD) are limited because the patients' reduced glomerular filtration rate results in the accumulation of certain drugs and/or their metabolites. Although recommended oral antidiabetic agents for patients with CKD differ between countries, all of the currently available dipeptidyl peptidase-4 (DPP-4) inhibitors can be used in not only patients with CKD but also patients with end-stage kidney disease on dialysis, and these inhibitors' use is increasing. Numerous clinical trials have shown that DPP-4 inhibitors provide effective and consistent glycemic control with a good tolerability profile and without severe hypoglycemia or weight gain. The glucose-lowering effect of DPP-4 inhibitors in diabetic patients with CKD is similar to the changes seen when DPP-4 inhibitors are prescribed to patients without CKD. Therefore, kidney function is unaffected by treatment with DPP-4 inhibitors. Moreover, DPP-4 inhibitors reduce the levels of glycated albumin, which is a better indicator of glycemic control than glycated hemoglobin is, without hypoglycemia in patients with end-stage kidney disease undergoing dialysis. Furthermore, it has been suggested that DPP-4 inhibitors might have a kidney-protective effect since they can potentially reduce the incidence of albuminuria. Although these results suggest that DPP-4 inhibitors can protect against diabetic nephropathy, insufficient evidence is available to conclude that this class of agent directly prevents or decreases nephropathy in humans independently from improved glucose control. Further long-term studies are needed to address whether DPP-4 inhibitors reduce the development and progression of diabetic nephropathy and improve cardiovascular outcomes in diabetic patients with CKD. Here, we describe the clinical efficacy and safety of DPP-4 inhibitors for patients with CKD, including those receiving dialysis.