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

Abstract

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.

Keywords:

• dipeptidyl peptidase-4 inhibitors
• insulin
• add-on therapy
• diabetes mellitus
• meta-analysis

Disclosure

The authors report no conflicts of interest in this work.