Assessing the therapeutic potential of Tirzepatide in modulating inflammatory responses and mitigating acute pancreatitis

Background Acute pancreatitis (AP) is a severe inflammation of the pancreas, marked by elevated enzyme levels, cellular inflammation, and necrosis. Recent studies emphasize the critical role of inflammation in AP progression. Tirzepatide, a multi‐target agonist of glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) receptors, has demonstrated notable anti‐inflammatory and metabolic benefits. Methods This study explores the therapeutic potential of Tirzepatide in pancreatitis induced by L‐arginine in rats, focusing on enzymatic markers, cytokine profiles, oxidative stress, and histological outcomes. Over 27 days, rats were distributed into Control, Tirzepatide, L‐Arginine, and L‐Arginine + Tirzepatide groups, with the latter receiving L‐Arginine to induce pancreatitis followed by Tirzepatide administration. Results L‐Arginine significantly elevated serum amylase, lipase, and inflammatory mediators (IL‐6, IL‐4, and IL‐10), alongside oxidative stress markers and histopathological deterioration. Conversely, the L‐Arginine + Tirzepatide group exhibited reduced lipase and IL‐6 levels, suppressed reactive oxygen species (ROS) generation, and enhanced anti‐inflammatory cytokines IL‐4 and IL‐10. Histopathological analysis revealed reduced necrosis and tissue damage in the L‐Arginine + Tirzepatide group compared to the L‐Arginine group, indicating Tirzepatide's possible protective effects. Immunofluorescence studies further demonstrated increased p‐Akt expression, supporting the role of Tirzepatide in cellular repair and recovery. Conclusion These findings highlight Tirzepatide's ability to mitigate pancreatic damage through antioxidant and anti‐inflammatory mechanisms, underscoring its potential as a pharmacological agent for acute pancreatitis.