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.