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Diabetes Res Clin Pract. 2014 Mar;103(3):395-401. doi: 10.1016/j.diabres.2013.12.039. Epub 2014 Jan 3.

The dipeptidyl peptidase-4 inhibitor vildagliptin does not affect ex vivo cytokine response and lymphocyte function in patients with type 2 diabetes mellitus.

Author information

1
Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. Electronic address: p.vanpoppel@aig.umcn.nl.
2
Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The Netherlands.
3
Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
4
Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Abstract

AIMS:

The enzyme dipeptidyl peptidase-4 (DPP-4) is a key player in the degradation of incretin hormones that are involved in glucose metabolism. DPP-4 is also expressed on immune cells and is associated with several immunological functions. Some studies have reported increased rates of infections in patients treated with DPP-4 inhibitors. We therefore assessed whether treatment with the DPP-4 inhibitor vildagliptin affected cytokine production and T-cell differentiation.

METHODS:

Patients with type 2 diabetes were treated with vildagliptin or an active comparator, acarbose, for four weeks, in a randomized cross-over trial. Blood was sampled at the end of each treatment period and peripheral blood mononuclear cells were isolated and stimulated with a broad spectrum of pattern recognition receptor agonists.

RESULTS:

Serum cytokine concentrations and ex vivo cytokine production (both monocyte and T-cell derived) did not differ during treatment with vildagliptin compared to acarbose. Similarly, ex vivo relative upregulation of mRNA transcription of T-cell lineage specific transcription factors was unaffected by vildagliptin treatment.

CONCLUSIONS:

These data show that a four-week treatment with vildagliptin in patients with type 2 diabetes mellitus does not result in a significant modulation of cytokine responses. This observation suggests that inhibition of DDP-4 does not lead to an increased risk of infection by diminishing cytokine production.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01000688.

KEYWORDS:

DPP-4 inhibitor; Immune function; Side effects; Type 2 diabetes

PMID:
24485397
DOI:
10.1016/j.diabres.2013.12.039
[Indexed for MEDLINE]
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