Sitagliptin reduces cytokine-induced β-cell apoptosis in prediabetes: A six-month interventional study

Islet inflammation, initiated by macrophage infiltration, which activates nuclear factor-kappa B (NF-κB), plays a crucial role in the early stage of diabetes. The study aimed to assess how initial treatment with sitagliptin affects inflammation-driven β-cell apoptosis by measuring plasma levels of Fas, Fas Ligand (Fas-L), and Interleukin-1β (IL-1β) in prediabetes.

This prospective interventional study included 56 treatment-naïve patients with impaired fasting glucose (IFG). Participants received either 50 mg sitagliptin twice daily or 100 mg sitagliptin once daily for 6 months. Plasma levels of inflammatory apoptotic markers (Fas, Fas-L, and IL-1β) were measured by ELISA at baseline and after 6 months of treatment. Wilcoxon signed-rank test was used to evaluate changes in biomarker levels. Hierarchical multiple regression analysis was conducted to identify predictors associated with improved β-cell function, as assessed by HOMA-B.

After 24 weeks of treatment, significant reductions were observed in plasma levels of Fas, Fas-L, and IL-1β (p < 0.001). Glycemic parameters also improved significantly (p < 0.001). Regression analysis levels were strong negative predictors of HOMA-B (R² = 29.8 %, p < 0.001) and remained significantly associated with improved HOMA-B after treatment (R² = 73.8 %, p = 0.000), with additional contribution from IL-1β.

Sitagliptin demonstrates promising therapeutic effects in prediabetes by reducing inflammation-induced β-cell apoptosis. Its potential to suppress pro-apoptotic cytokines underscores its role as an early therapeutic approach.