77-LB: A Novel Glucagon-Like Peptide-1 (GLP-1R) and Glucagon (GCGR) Receptor Dual Agonist, Mazdutide (IBI362), Attenuates Hyperuricemia in Hyperuricemic Rats

Introduction: Existing studies have not conclusively proven that GLP-1RA drugs can attenuate hyperuricemia, and dual agonist drugs such as Tirzepatide have also not been reported. But in previous studies, we unexpectedly found that the statistically significant reduction in serum uric acid levels in participants receiving Mazdutide. So we designed animal experiments to verify this result. Methods: Male 12-week-old adult SD rats were given potassium oxyzincate 1000 mg/kg and adenine 100 mg/kg used to maintain hyperuricemia status and were divided into different groups (Table1). Statistical and metabolomic, proteomic, and phosphoproteomic analyses were performed after 18 days of intervention, respectively. Results: The Mazdutide and allopurinol groups showed varying degrees of decrease in serum uric acid, while there was no change in the semaglutide group (Table1). The specific mechanism will be analyzed after the histological results are available. Conclusion: The degree of reduction of hyperuricemia by Mazdutide on rats was comparable to that of allopurinol. A slight increase in UUA may mean that the drug is working by promoting uric acid excretion. We conclude that Mazdutide has a safety and effectiveness profile similar to GLP-1 receptor agonist and has potential therapeutic benefit in the treatment of hyperuricemia. Disclosure H. Jiang: None. Y. Zhang: None. Y. Ren: None. Funding First Affiliated Hospital; College of Clinical Medicine of Henan University of Science and Technology