Dipeptidyl peptidase-4 inhibitors as add-on therapy to insulin in patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled trials

Purpose: Addition of the dipeptidyl peptidase-4 (DPP4) inhibitors to insulin in patients with type 2 diabetes mellitus (T2DM) may achieve better glycemic control. However, results of pilot randomized controlled trials (RCTs) are inconsistent. We aimed to perform a meta-analysis of RCTs to evaluate efficacy and safety of DPP4 inhibitors compared with placebo/no treatment as add-on therapy to insulin in T2DM patients. Materials and methods: Relevant studies were identified via a search of PubMed, Cochrane Library, and Embase databases. A fixed or random effect model was applied according to the heterogeneity. Results: Overall, 22 RCTs with 6,957 T2DM patients were included. Addition of DPP4 inhibitors to insulin was associated with significantly reduced HbA1c as compared with controls (weighed mean difference [WMD]: -0.54%, p<0.001). The benefits of DPP4 inhibitors as add-on therapy on HbA1c were independent of study design, follow-up duration, categories of DPP4 inhibitors used, and using of fixed/adjustable insulin doses as indicated by predefined subgroup analyses. Moreover, addition of DPP4 inhibitors to insulin was associated with significantly reduced fasting blood glucose (WMD: -0.47mmol/L, p<0.001), postprandial glucose at 2 hrs (WMD: -2.03 mmol/L, p<0.001), and daily dose of insulin (WMD: -2.73U/d, p<0.001), while body weight (WMD: 0.02 g, p=0.81) or risk of symptomatic hypoglycemia (risk ratio: 0.92, p=0.37) were not affected. Conclusions: Addition of DPP4 inhibitors to insulin significantly improved the glycemic control in T2DM patients without further increasing the risk of weight gain and hypoglycemia.