Efficacy and Safety of DPP-4 Inhibitors and Metformin Combinations in Type 2 Diabetes: A Systematic Literature Review and Network Meta-Analysis

Abstract

Objective

Several oral antidiabetic regimens are available for treating type 2 diabetes mellitus (T2DM), dipeptidyl peptidase-4 inhibitors (DPP4i) being one of them. We conducted a network meta-analysis (NMA) comparing DPP4i plus metformin (Met) combination with other Met-based oral antidiabetic drug (OAD) combinations used in treating patients with T2DM.

Methods

We searched PubMed and Embase from inception until 19th April, 2022 for phase II and phase III trials in patients with T2DM on Met-based traditional OADs. The primary outcome was assessed by change in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and 2-hour post-prandial blood glucose (2h-PPG). The secondary safety outcomes assessed were hypoglycemic events, serious adverse events (SAEs), cardiovascular (CV) events, and gastrointestinal (GI) events.

Results

Sixty-two trials were included in the analysis. The combination of DPP4i + Met revealed a comparable mean reduction in HbA1c levels to the glinides (Gli) + Met combination (mean difference [MD]: −0.03%, 95% CI: 0.69, −0.65), although the difference was not statistically significant. The mean HbA1c reduction with DPP4i + Met was greater than with sulfonylureas (SU) + Met (MD: −0.05, 95% CI: −0.29, 0.39), thiazolidinedione (TZD) + Met (MD: −0.69, 95% CI: −1.39, −0.02), and SU + TZD (MD: 0.21; 95% CI: −1.30, 1.71), with no statistical significance. DPP4i + Met demonstrated a non-significant lower incidence of CV events in comparison to TZD + Met (RR: 1.01, 95% CI: 0.46, 2.45) and SU + Met (RR: 1.06, 95% CI: 0.61, 2.06).

Conclusion

DPP4i in combination with Met was efficacious and had a well-tolerated safety profile compared with other traditional OADs. This combination can be considered as a suitable treatment option for patients with T2DM.

Keywords:

• dipeptidyl peptidase-4 inhibitors
• efficacy
• safety
• metformin
• type 2 diabetes mellitus

Data Sharing Statement

The data used to support the findings of this study are available from the corresponding author upon request.

Ethics Approval and Informed Consent

Not applicable: no ethical approval was required as this study is a meta-analysis and involves the collection of data from published literature.

Acknowledgments

The authors would like to acknowledge Anwesha Mandal and Dr. Amit Bhat of Indegene Ltd, India, for their editorial and medical writing support. In addition, the authors extend their thanks to Ashwini Patil of Indegene Ltd, India, for statistical inputs and analysis support.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no conflicts of interest in this work.

Additional information

Funding

This study was funded by AstraZeneca China in accordance with Good Publication Practice (GPP3) guidelines.