Comparative Toxicological Evaluation of Pioglitazone and Glimepiride in Wistar Rats

Introduction: Diabetes mellitus is one of the most common endocrine disorders and affects the body’s ability to produce or effectively utilize insulin. It is characterized by persistent hyperglycemia caused either by insufficient insulin secretion or by the body’s reduced response to insulin at the cellular level. Glimepiride, a second-generation sulfonylurea, and pioglitazone hydrochloride, a thiazolidinedione, are widely prescribed for the management of blood glucose levels in patients with diabetes mellitus. However, their potential adverse effects require further investigation. This experimental study aims to compare the degree and nature of toxicity associated with glimepiride and pioglitazone, while providing a clearer understanding of their safety profiles and potential risks. Methods: This study was conducted on 18 male Wistar albino rats (Rattus norvegicus), aged 10-12 weeks and weighing 216-260 g. The animals were randomly allocated into three experimental groups: control, glimepiride-treated, and pioglitazone-treated, with six animals in each group. All animals were housed under laboratory conditions with free access to food and water. Results: There was no statistically significant difference in serum urea levels between the control and treatment groups (p > 0.05). Serum creatinine levels were significantly decreased in the glimepiride-treated group compared with the control group (p < 0.05), whereas no significant difference was observed in the pioglitazone hydrochloride-treated group (p > 0.05). Alkaline phosphatase (ALP) activity differed significantly between the pioglitazone hydrochloride and glimepiride groups, as well as between the glimepiride and control groups (p < 0.05). Alanine aminotransferase (ALT) activity showed a statistically significant difference among all three groups (p < 0.05). Aspartate aminotransferase (AST) activity was significantly elevated in the glimepiride-treated group compared with both the control and pioglitazone hydrochloride-treated groups (p < 0.05), whereas no significant difference was observed between the pioglitazone hydrochloride-treated and control groups (p > 0.05). No significant differences in serum uric acid levels were detected among the study groups (p > 0.05). A significant difference in serum albumin levels was observed between the control and pioglitazone hydrochloride-treated groups, as well as between the glimepiride- and pioglitazone hydrochloride-treated groups (p < 0.05). Histopathological examination revealed no significant structural alterations in the examined tissues. Conclusion: Both pioglitazone hydrochloride and glimepiride produced measurable biochemical changes without causing any significant histopathological alterations in tissues of non-diabetic healthy rats. The findings suggest subclinical effects rather than overt organ toxicity. Glimepiride demonstrated a slightly more favorable profile to pioglitazone hydrochloride regarding effects on some biomarkers.