Effect of dipeptidyl peptidase-4 inhibitors on circulating tumor necrosis factor-α concentrations: A systematic review and meta-analysis of controlled trials

Stephen Atkin, Niki Katsiki, Maciej Banach, Dimitri P. Mikhailidis, Matteo Pirro, Amirhossein Sahebkar

Research output: Contribution to journalReview article

14 Citations (Scopus)


Objective Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes mellitus. There are also reports of an effect of these drugs in reducing inflammation through inhibition of tumor necrosis factor-α (TNF-α) that is an important mediator for several inflammatory processes. The present systematic review and meta-analysis were performed to evaluate the effect of DPP-4 inhibitors on circulating TNF-α levels in T2DM patients. Methods A systematic review and a meta-analysis were undertaken on all controlled trials of DPP-4 inhibitors that included measurement of TNF-α. The search included PubMed-Medline, Scopus, ISI Web of Knowledge and Google Scholar databases. Quantitative data synthesis was performed using a random-effects model, with standardized mean difference (SMD) and 95% confidence interval (CI) as summary statistics. Meta-regression and leave-one-out sensitivity analysis were performed to assess the modifiers of treatment response. Results Eight eligible articles (6 with sitagliptin and 2 with vildagliptin) comprising 9 treatment arms were selected for this meta-analysis. Meta-analysis suggested a significant reduction of circulating TNF-α concentrations following treatment with DPP-4 inhibitors (SMD: − 1.84, 95% CI: − 2.88, − 0.80, p = 0.001). The effect size was robust in the sensitivity analysis and not mainly driven by a single study. A subgroup analysis did not suggest any significant difference between the TNF-α-lowering activity of sitagliptin (SMD: − 1.49, 95% CI: − 2.89, − 0.10) and vildagliptin (SMD: − 2.80, 95% CI: − 4.98, − 0.61) (p = 0.326). Conclusion This meta-analysis of the 8 available controlled trials showed that DPP-4 inhibition in patients with type 2 diabetes mellitus was associated with significant reductions in plasma TNF-α levels with no apparent difference between sitagliptin and vildagliptin.

Original languageEnglish
Pages (from-to)1458-1464
Number of pages7
JournalJournal of Diabetes and its Complications
Issue number9
Publication statusPublished - 1 Sep 2017



  • Diabetes
  • DPP-iv
  • Inflammation
  • Meta-analysis
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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