Effects of empagliflozin on interleukin-23 secretion from peripheral blood mononuclear cells in patients with type 2 diabetes versus healthy subjects: an in vitro study.

Background and objectives: Chronic inflammation is a critical contributor to the pathogenesis of type 2 diabetes mellitus (T2DM). Interleukin-23 (IL-23) is recognized as a key pro-inflammatory cytokine involved in immune dysregulation. Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, has been shown to exert anti-inflammatory effects; however, its specific influence on IL-23 production in peripheral blood mononuclear cells (PBMCs) remains unclear. This study aims to evaluate the impact of empagliflozin on IL-23 secretion in PBMCs isolated under in vitro conditions.

Methods: This in vitro case-control study was conducted in Iran in 2024 and included 50 participants (23 males and 27 females), comprising 25 individuals with T2DM and 25 age- and sex-matched healthy controls. Blood samples were collected from all participants to assess fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels. In vitro, empagliflozin was added to the blood samples at a concentration of 100 µg/mL. IL-23 levels were measured in both groups before and after treatment with empagliflozin. Statistical analyses were conducted using SPSS version 21.

Results: Statistical analysis revealed that IL-23 secretion from PBMCs cultured with empagliflozin was significantly reduced compared to untreated cultures in both individuals with T2DM (p < 0.001) and healthy controls (p = 0.048). Baseline IL-23 levels were significantly higher in the T2DM group compared to the control group, and this difference remained significant following empagliflozin treatment (p = 0.021). Moreover, the magnitude of empagliflozin's effect on IL-23 secretion differed significantly between the two groups (p = 0.016). In the T2DM group, IL-23 secretion showed a positive correlation with FBG and HbA1c levels in the absence of empagliflozin; however, these correlations were weak or non-significant following treatment. No significant correlations were observed in the control group under either condition.

Conclusion: Empagliflozin significantly reduces IL-23 secretion in both T2DM patients and healthy individuals, with a more pronounced effect observed in those with T2DM. These findings suggest that empagliflozin may exert anti-inflammatory effects independent of glycemic control, underscoring its potential role in mitigating immune dysregulation and chronic inflammation in T2DM.