Evaluation of The Antioxidant, Hypolipidemic, and Pancreatic Histological Alterations Effects of Tirzepatide in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Rats

Background: Type 2 diabetes mellitus (T2DM) is a complicated and multifaceted metabolic disease defined by insulin resistance, dyslipidemia, oxidative stress, and β-cell dysfunction. Tirzepatide (TZP), a dual GIP and GLP-1 receptor agonist, offers potent glucose-lowering and weight-loss. Objective: To assess the effect of different doses of TZP on lipid profile, SOD activity, and histopathological changes of the pancreas in a high-fat diet and streptozotocin-induced T2DM. Methods: Thirty male Wistar rats were divided into five groups (n=6): Group I, control group, Groups II-V were induced with diabetes by feeding with a high-fat diet for six weeks with a single injection of streptozocin (35 mg/kg). Groups III- V were treated with TZP at three doses: low, medium, and high (0.44, 0.88, and 1.32 mg/kg) subcutaneously once weekly for 4 weeks. Blood and pancreas samples were then collected for biochemical and histopathological analyses. Result: The results showed that all doses of TZP-treated groups significantly lowered (p<0.0001) cholesterol, TG, LDL, and VLDL, and increased SOD and HDL levels in a dose-response manner compared to the T2DM rats. while all doses of the TZP-treated groups revealed pronounced improvements in pancreatic architecture, especially at the higher doses. Conclusion: Treatment of T2DM rats with TZP ameliorated their lipid profile, improving pancreatic architecture and augmenting antioxidant activity.