Sitagliptin, a DPP-4 Inhibitor, Alters the Subsets of Circulating CD4+ T Cells in Patients with Type 2 Diabetes

Objective: CD26/DPP-4 is highly expressed by T cells, especially CD4+ T cells (T helper cells; Th) and may regulate the differentiation, maturation, or proliferation of these cells. We investigated the effects of sitagliptin, a DPP-4 inhibitor, on the absolute number and percentage of various subsets of circulating CD4+ T cells in patients with type 2 diabetes.

Methods: We enrolled 30 consecutive patients (16 women and 14 men) with type 2 diabetes in a prospective, randomized, open-label, blinded endpoint study. Eligible participants were randomly assigned at a 2:1 ratio to either a sitagliptin group (sitagliptin at 50mg/day) or an active control group (glimepiride at 1mg/day). Patients were followed for 12 weeks with monthly review. Peripheral blood mononuclear cells were examined by flow cytometry for intracellular expression of cytokines (IFN-γ as a marker of Th1cells, IL-4 for Th2 cells, and IL-17 for Th17 cells) and for expression of CD4, CD25, and Foxp3 (regulatory T cells [Treg]).

Results: Both groups showed similar improvement of glycemic control. The total number of CD4+ T cells was decreased by treatment with sitagliptin, while it did not change in the control group. The number and percentage of Th17 cells and Treg cells both decreased significantly in the sitagliptin group, but not in the control group. There was a significant positive correlation between changes in the percentage of Th17 cells and Treg cells after treatment with sitagliptin.

Conclusions: Treatment with sitagliptin for 12 weeks reduced the number of circulating CD4+ T cells, especially Th17 and Treg cells, in patients with type 2 diabetes.