A dual in silico-in vitro assessment of nine glimepiride apis: efficacy and oxidative stress protection in type 2 diabetes.

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired glucose metabolism. Glimepiride, a sulfonylurea drug, is commonly used to manage blood glucose levels in T2DM patients. However, the efficacy of various active pharmaceutical ingredients (APIs) of Glimepiride has not been thoroughly compared. Here, we systematically evaluate nine Glimepiride APIs for their modulation of oxidative stress pathways via computational and laboratory models. Molecular docking simulations were performed to investigate the binding affinity between Glimepiride and aldose reductase (AR), revealing a strong binding interaction. Furthermore, High-Performance Liquid Chromatography analysis was conducted to assess the purity of the APIs, showing consistent results with all samples exceeding 99.5% purity. In vitro experiments were performed using liver enzymes extracted from diabetic rats to assess the effects of the nine APIs of Glimepiride on AR and glutathione reductase (GR) activity. Significant variations in AR inhibition and GR activation were observed among the APIs. In particular, compound G1 exhibited potent AR inhibition and a marked reduction in MDA levels, highlighting its strong antioxidant potential. Meanwhile, compound I2 was the most effective at activating GR, suggesting a potential role in enhancing the natural antioxidant defences. These results support the therapeutic potential of Glimepiride in mitigating oxidative stress and its beneficial effects on key metabolic enzymes in T2DM. The observed differences in the efficacy of the Glimepiride APIs were likely due to factors such as variations in bioavailability, formulation composition, and pharmacokinetic properties. The findings highlight the importance of assessing these factors when evaluating generic formulations for therapeutic use in T2DM management.