A systematic review of the benefits and harms of dipeptidyl peptidase‐4 inhibitor for chronic kidney disease

Introduction: Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD) and the optimal glycemic control is key to delay the progression of the disease and prevent major complications. Dipeptidyl peptidase‐4 (DPP‐4) inhibitors have emerged as a promising therapeutic option. However, the benefits and harms of the treatment have yet to be clarified for diabetic patients with CKD. Methods: Type 2 diabetic patients with moderate to severe CKD including end‐stage renal disease were eligible and randomized controlled trials comparing DPP‐4 inhibitors with no treatment or placebo or other antihyperglycemic agents were included. A systematic electronic search was conducted through the Medline Ovid, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov. Findings: Six placebo/open and 2 active controlled trials (1747 participants) were included. The adjusted mean difference of hemoglobin A_1c between DPP‐4 inhibitors and placebo ranged from ?0.60% to ?0.42%. The odds ratio of hypoglycemia, mortality and severe adverse effects due to all types of DPP‐4 inhibitors were 1.35 (95% CI: 0.98–1.84), 0.88 (95% CI: 0.42–1.86) and 0.86 (95% CI: 0.65–1.15), respectively while that due to DPP‐4 inhibitors with renal clearance were 1.40 (95% CI: 0.87 to 2.24), 0.85 (95% CI: 0.35 to 2.04) and 0.91 (95% CI: 0.63 to 1.32), respectively. Discussion: DPP‐4 inhibitors demonstrated beneficial effects on the glycemic control for diabetic patients with CKD without causing any additional adverse effects. However, a definitive conclusion has yet to be drawn due to serious methodological problems and a small number of studies.