Transient Increase in Serum Uric Acid and Gout attacks after weight loss effect on Tirzepatide and Semaglutide

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1) and dual glucosedependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists (GIP/GLP-1) are increasingly used for weight reduction and metabolic improvement.Although sustained weight loss is generally associated with reduced serum uric acid (UA) levels, transient hyperuricemia has been described following bariatric surgery and rapid catabolic states.Data regarding UA changes during pharmacologically induced weight loss remain limited.Methods: We report a case series of four adults who developed elevated UA levels and/or acute gout flares following significant weight loss induced by GLP-1 RA or dual GIP/GLP-1 RA therapy.Results: Three of four patients demonstrated a consistent rise in UA levels within 3-5 months of therapy initiation, irrespective of baseline UA status.Two patients experienced acute gout flares, including one with recurrent episodes despite uratelowering therapy and normal UA levels.All patients achieved substantial weight loss and marked improvement in glycemic and lipid profiles.Despite favorable metabolic changes, UA levels remained elevated or worsened during follow-up.No patient had undergone surgery or experienced clinical dehydration, suggesting mechanisms distinct from postoperative hyperuricemia.Conclusion: Rapid weight loss may induce transient hyperuricemia through ketosisrelated alterations in renal urate handling.This mechanism parallels observations in fasting and ketogenic states and may explain the paradoxical rise in UA despite overall metabolic improvement.J o u r n a l P r e -p r o o f GLP-1 RA-and dual GIP/GLP-1 RA-induced rapid weight loss may be associated with transient elevations in UA and gout flares.Clinicians should consider monitoring UA levels during early therapy, particularly in patients with prior hyperuricemia or gout.