Pharmacodynamic Interactions of Repaglinide and Piperine in Modulating Glycemic Control and Insulin Sensitivity in Streptozotocin-Induced Diabetic Rats

Background: Combination therapies are often needed to achieve optimal glycemic control and improve INS sensitivity in DM management. An INS secretagogue, RPG, and a natural bioactive phenolic compound with multifunctional pharmacological roles, PIP, have been tested with encouraging results in diabetic patients individually. This study examined the synergistic effects of combination therapy in STZ-induced diabetic rats. Materials and Methods: Normal rats were kept as control (vehicle) and STZ-induced diabetic rats were divided into four groups, namely, control (vehicle), RPG-treated, PIP-treated, and a combination of RPG and PIP. Single and multiple doses were administered for a certain period. Blood glucose level, INS secretion, HOMA-IR, C-peptide level, and glucagon level were the key parameters measured in this study. Pancreatic histopathology was also performed to check the status of β-cell integrity. Results and Discussion: The administration of RPG combined with PIP led to a significant decrease in blood glucose levels and a proportional rise in INS production compared to the groups receiving individual treatment. Combined therapy also increased INS sensitivity, as reflected by lower HOMA-IR scores. Moreover, in the combination group, C-peptide levels were higher, while glucagon levels were lower, reflecting an improvement in the overall glycemic profile. Histopathological examination showed that combination therapy preserved more intact β-cell architecture than either treatment alone, hence protecting pancreatic function. Conclusion: The combination of RPG and PIP is more effective in enhancing glycemic control and INS sensitivity in STZ-induced diabetic rats than either agent alone. These findings suggest that combination therapy could be a novel approach toward managing DM and thus might improve clinical outcomes in these patients.