Evaluation of the Effect of Empagliflozin Therapy on T Helper 22 Cell-Related Factors in Patients with Type 2 Diabetes Mellitus

The increased response of T helper (Th) 22cells might be involved in thepathogenesis ofType 2 Diabetes Mellitus (T2DM). The present study aimed to investigate the transcription factor of Th22 cells (aryl hydrocarbon receptor [AHR]) and interleukin 22 (IL-22) in CD4+ T cells as well as the impact of oral empagliflozin treatment. The correlation between the aforementioned factors and clinical parameters was also determined among the patients.

In this case-control study, 50 patients under the treatment of metformin and gliclazide were divided into two equal groups, including the patients receiving empagliflozin (EMPA+) and not receiving empagliflozin (EMPA, as the control group). The peripheral blood CD4+ T cells were isolated on the initiation day of the study and after 6 months of therapy, and the gene expression levels of AHR and IL-22 were evaluated by real-time polymerase chain reaction. In addition, the production of IL-22 after activation was measured using enzyme-linked immunosorbent assay.

The levels of fasting plasma glucose and hemoglobin A1c diminished in the EMPA+ group after empagliflozin therapy, compared to those reported at the baseline (initiation day; P<0.001 and P=0.04). The gene expression level of IL-22 and production of IL-22 significantly reduced after 6 months of empagliflozin therapy (P=0.011 and P=0.001). A significant positive correlation between IL-22 production and its gene expression with AHR as well as between fasting plasma glucose and hemoglobin A1c was observed in the EMPA+ patients after therapy (P˂0.05).

In addition to antidiabetic effects, empagliflozin has anti-inflammatory impacts on the immune system, especially on Th22 cell-related factors.