Efficacy and safety of dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes mellitus patients with moderate to severe renal impairment: a meta-analysis

OBJECTIVE: Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral antidiabetic agents for type 2 diabetes mellitus (T2DM) patients. However, the effects and safety of DPP-4 inhibitors in T2DM patients with renal impairment (RI) remain controversial. Therefore, we conducted this meta-analysis to assess the efficacy and safety of DPP-4 inhibitors in T2DM patients with moderate to severe RI. MATERIALS AND METHODS: The PubMed, Embase, and Web of Science database were searched for published randomized controlled trials (RCTs), which compared DPP-4 inhibitors with placebo or a control regimen. A fixed-model effect or random-effect model was used to assess the effects of DPP-4 inhibitors on T2DM patients with RI. Subgroup analysis or meta-regression analysis were performed to explore the potential sources of heterogeneity among the included studies. RESULTS: 13 RCTs with a total of 2,940 patients were included in this meta-analysis. Compared with other treatments, DPP-4 inhibitors were associated with a greater change in HbA1c level (weight mean difference (WMD)=-0.50, 95% CI: -0.61, -0.39; p<0.001), and a higher response rate of patients achieving the HbA1c goal of <7% (risk ratio (RR)=1.38, 95% CI: 1.12, 1.70; p=0.002). Subgroup analysis suggested that the reduced HbA1c was observed in all types of DPP-4 inhibitors, and in patients with moderate or severe RI, but not in those with end-stage renal disease. DPP-4 inhibitors did not significantly lower the FPG level (WMD=-0.36, 95% CI: -0.92, 0.20; p=0.204), and this was seen in all types of DPP-4 inhibitors except gemigliptin, which showed a significant reduction in FPG level. The prevalence of adverse events (RR=0.98, 95% CI: 0.94, 1.02; p=0.256) in the two groups was not significantly different, and DPP-4 inhibitors did not induce a higher rate of hypoglycemia (RR=1.31, 95% CI: 0.97, 1.77; p=0.075). CONCLUSIONS: DPP-4 inhibitors significantly lowered HbA1c levels in T2DM patients with moderate to severe RI. And the treatment of DPP-4 inhibitors did not increase the risk of hypoglycemia and adverse events. Considering the potential limitations in this meta-analysis, more large-scale, well-conducted RCTs are needed to identify our findings.