Effects of DPP4 Inhibitors on Renal Outcomes in Diabetes Mellitus: A Systematic Review and Meta-Analysis

OBJECTIVES: This meta-analysis of randomized clinical trials (RCT) intends to evaluate the efficacy of DPP4 Inhibitors (DPP4I) compared with placebo, other antidiabetics (or DPP4I) on renal outcomes, adverse events (AEs), and all-cause mortality. METHODS: We searched relevant scientific database for RCTs with DPP4I and prespecified renal end point. The effect size (mean difference or risk ratio) was reported with its 95% confidence interval. RESULTS: Eight RCTs (n = 39040 participants) were included in the analysis. The rate of change in eGFR was not different in DPP4 inhibitor and control group. DPP4I use beyond 52 weeks did not worsen albuminuria progression (RR 0.88; 95% CI 0.80 to 0.96; high quality evidence) compared to placebo. The risk of AEs within 52 weeks (RR 0.93; 95% CI 0.80 to 1.08; moderate quality evidence), beyond 52 weeks (RR 0.98; 95% CI 0.97 to 1.00; low quality evidence), and all-cause mortality (RR 1.04; 95% CI 0.96 to 1.12; very low quality evidence) were similar to placebo. In head-to-head comparison between two DPP4I studies, no significant differences were found between alogliptin and vildagliptin for improvement in eGFR, UACR, or AE at 24 weeks. CONCLUSIONS: DPP4I do not seem to provide persuasive benefit in the renal outcomes or all-cause mortality in diabetes mellitus, though there was no evidence for increased AEs.