Network meta-analysis of liraglutide versus dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes in Japanese patients

Abstract

Aims: To determine the comparative efficacy and safety of liraglutide and dipeptidyl peptidase-4 (DPP-4) inhibitors as antidiabetics for Japanese patients with uncontrolled type 2 diabetes (T2DM).

Methods and materials: We searched for randomized controlled trials (RCTs) evaluating outcomes among Japanese adults with uncontrolled T2DM and including liraglutide or DPP-4 inhibitors up to August 2016. We extracted data on trial and patient characteristics, and the following outcomes: HbA1c, weight, patients meeting HbA1c <7%, patients experiencing hypoglycemic events, microalbuminuria, estimated glomerular filtration rate (eGFR) and creatinine. We synthesized data using network meta-analyses (NMA) using a Bayesian framework. Continuous outcomes were modeled using normal likelihoods and an identity link, while dichotomous outcomes were modeled using a binomial likelihood and a logit link.

Results: The systematic literature review yielded 39 publications pertaining to 38 trials. A total of 27 trials (5032 patients) reported change in HbA1c at 12 weeks and at 24 weeks 9 trials (2091 patients). All treatments showed statistically significant reductions in HbA1c relative to placebo at 12 and 24 weeks. Liraglutide 0.9 mg was statistically superior to all DPP-4 interventions (vildagliptin, sitagliptin, linagliptin, alogliptin, teneligliptin, trelagliptin and omarigliptin) at 12 weeks and 24 weeks among those reporting. Treatments were not statistically differentiable with respect to weight change and risk of hypoglycemia. Finally, no comparisons of eGFR and microalbuminuria were conducted, as this data was reported in too few trials to conduct analyses.

Limitations: Some important outcomes were limited by poor reporting (eGFR and microalbuminuria) or low event rates (hypoglycemia). The follow-up time was relatively short. Clinically, the 24 week time point is more important as it demonstrates more sustained results.

Conclusions: Our research suggests that liraglutide 0.9 mg offers a more efficacious treatment option for T2DM than the DPP-4 inhibitors among adult Japanese patients and that it is a viable option for this population.

Keywords:

• Type 2 diabetes mellitus
• network meta-analysis
• glucagon-like peptide-1 receptor agonists
• dipeptidyl peptidase-4 inhibitors
• HbA1c
• Japan

Transparency

Declaration of funding

This study was sponsored by Novo Nordisk. The sponsor contributed to the design of the study, but did not have a role in the analysis or interpretation. The manuscript was drafted by Precision Health Economics and approved by the sponsor.

Author contributions: D.A. and S.K. had full access to all of the data in the study. D.A. takes responsibility for the integrity of the data, the accuracy of the data analysis, and the final decision to submit for publication. Study concept and design: N.K., D.A., S.K., and R.K. Acquisition, analysis, or interpretation of data: S.K., D.A., R.G. and M.H. Drafting of the manuscript: D.A., S.K. and N.K. Critical revision of the manuscript for important intellectual content: D.A., S.K., R.G., M.H., R.K. and N.K. Statistical analysis: D.A. and S.K. Obtained funding: N.K. Administrative, technical, or material support: N.K. and S.K. Study supervision: N.K. and S.K.

Declaration of financial/other relationships

D.A., S.K., R.G. and M.H. have disclosed that they are paid employees of Precision Health Economics, which has received compensation from Novo Nordisk for this work. N.K. has disclosed that she is an employee and shareholder of Novo Nordisk A/S. R.K. has disclosed that he is an employee of Novo Nordisk Pharma Ltd. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.

Acknowledgements

The authors would like to thank Melissa Barazandegan for assistance with data preparation, and Lucia Lorenzi for editorial assistance. Additionally, we would like to thank Jeroen Jansen for project guidance.