A dipeptidyl peptidase-4 inhibitor, sitagliptin, exerts anti-inflammatory effects in type 2 diabetic patients

Aims/hypothesis. Glucagon-like peptide-1 (GLP-1) exerts beneficial effects on the cardiovascular system. Here, we examined the effect of sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, on systemic inflammation and pro-inflammatory (M1)/anti-inflammatory (M2)-like phenotypes of peripheral blood monocytes in diabetic patients. Methods. Forty-eight type 2 diabetic patients were divided into the following two groups: sitagliptin-treatment (50 mg daily for 3 months) (n=24) and untreated control (n=24) groups. Measurements were undertaken to assess changes in glucose-lipid metabolism, serum levels of inflammatory cytokines such as serum amyloid A-LDL (SAA-LDL), C-reactive protein (CRP), interleukin-6 (IL-6), IL-10 and tumor necrosis factor-alpha (TNF-alpha). Furthermore, the effects of sitagliptin treatment on M1/M2-like phenotypes in peripheral blood monocytes were examined. Results. Treatment with sitagliptin significantly decreased fasting plasma glucose, hemoglobin A1c (HbA1c), serum levels of inflammatory markers, such as SAA-LDL, CRP, and TNF-alpha. In contrast, sitagliptin increased serum IL-10, an anti-inflammatory cytokine, as well as plasma GLP-1. In addition, sitagliptin increased monocyte IL-10 expression and decreased monocyte TNF-alpha expression. Multivariate regression analysis revealed that the sitagliptin treatment was the only factor independently associated with an increase in monocyte IL-10 (beta=0.499; R-2=0.293, P<0.05). However, other factors including the improvement of glucose metabolism were not associated with the increase. Conclusions/interpretation. This study is the first to show that a DPP-4 inhibitor, sitagliptin, reduces inflammatory cytokines and improves the unfavorable M1/M2-like phenotypes of peripheral blood monocytes in Japanese type 2 diabetic patients. (C) 2013 Elsevier Inc. All rights reserved.