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

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1458-1464
Number of pages7
JournalJournal of Diabetes and its Complications
Volume31
Issue number9
DOIs
Publication statusPublished - 1 Sep 2017

Fingerprint

Dipeptidyl-Peptidase IV Inhibitors
Meta-Analysis
Tumor Necrosis Factor-alpha
Confidence Intervals
Type 2 Diabetes Mellitus
Dipeptidyl Peptidase 4
PubMed
Therapeutics
Databases
Inflammation
Pharmaceutical Preparations
vildagliptin
Sitagliptin Phosphate

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Effect of dipeptidyl peptidase-4 inhibitors on circulating tumor necrosis factor-α concentrations : A systematic review and meta-analysis of controlled trials. / Atkin, Stephen; Katsiki, Niki; Banach, Maciej; Mikhailidis, Dimitri P.; Pirro, Matteo; Sahebkar, Amirhossein.

In: Journal of Diabetes and its Complications, Vol. 31, No. 9, 01.09.2017, p. 1458-1464.

Research output: Contribution to journalReview article

Atkin, Stephen ; Katsiki, Niki ; Banach, Maciej ; Mikhailidis, Dimitri P. ; Pirro, Matteo ; Sahebkar, Amirhossein. / Effect of dipeptidyl peptidase-4 inhibitors on circulating tumor necrosis factor-α concentrations : A systematic review and meta-analysis of controlled trials. In: Journal of Diabetes and its Complications. 2017 ; Vol. 31, No. 9. pp. 1458-1464.
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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.",
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AU - Banach, Maciej

AU - Mikhailidis, Dimitri P.

AU - Pirro, Matteo

AU - Sahebkar, Amirhossein

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N2 - 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.

AB - 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.

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KW - Tumor necrosis factor-α

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