Pioglitazone and Metformin on Improving Cognitive Dysfunction Caused by Diabetes Mellitus: A Comparative Study

Background and Objective: Diabetes mellitus is a common metabolic disease that impairs cognitive function. For diabetes management, different classes of drugs, including pioglitazone (PIO) and metformin (MET), are also reported to improve the cognitive dysfunction caused by diabetes. This study aims to compare the neuroprotective effect of PIO versus MET on diabetes mellitus (DM) induced cognitive dysfunction in rat models of diabetes. Materials and Methods: Six groups of sixty male albino rats (n = 10) were randomly created: Control, diabetes, MET, PIO, diabetes+MET and diabetes+PIO. Nicotinamide (120 mg kg(-1)) and streptozotocin (55 mg kg(-1)) intraperitoneal injections induced diabetes. The MET and PIO treatments lasted for 14 days. The survival rate, body weight, behavioral tasks (Y-maze, novel object recognition (NOR), elevated plus maze (EPM)) and glucose levels were measured after the completion of the treatments. Results: The findings elucidated that diabetes elicited a decrease in the survival rate, body weight and cognitive function, while concurrently provoking an increase in glucose levels. The groups that received PIO and MET exhibited enhancements in survival rate, cognitive function and glucose levels among the diabetic rats, although no significant changes were observed in body weight. Conclusion: This study revealed that PIO and MET improved cognitive dysfunction in diabetic rats, however, MET showed better effectiveness than PIO.