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

Abstract

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.

• Authors: Stephen L Atkin, Niki Katsiki, Maciej Banach, Dimitri P Mikhailidis, Matteo Pirro, Amirhossein Sahebkar
• Journal: Journal of diabetes and its complications (J Diabetes Complications) Vol. 31 Issue 9 Pg. 1458-1464 (Sep 2017) ISSN: 1873-460X [Electronic] United States
• PMID: 28647512 (Publication Type: Journal Article, Meta-Analysis, Review, Systematic Review)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Dipeptidyl-Peptidase IV Inhibitors
• Hypoglycemic Agents
• Nitriles
• Pyrrolidines
• Tumor Necrosis Factor-alpha
• Vildagliptin
• Adamantane
• Sitagliptin Phosphate

Topics

• Adamantane (analogs & derivatives, pharmacology, therapeutic use)
• Controlled Clinical Trials as Topic (statistics & numerical data)
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Dipeptidyl-Peptidase IV Inhibitors (pharmacology, therapeutic use)
• Humans
• Hypoglycemic Agents (pharmacology, therapeutic use)
• Nitriles (pharmacology, therapeutic use)
• Pyrrolidines (pharmacology, therapeutic use)
• Sitagliptin Phosphate (pharmacology, therapeutic use)
• Tumor Necrosis Factor-alpha (blood)
• Vildagliptin