Early urate-lowering therapy and cardiometabolic risk in adults without documented major cardiometabolic disease: a real-world cohort study

Background: Whether urate-lowering therapy (ULT) affects cardiometabolic outcomes in individuals without established metabolic disease remains uncertain. Materials and methods: This retrospective cohort study used TriNetX data (2015-2023) to include adults with newly diagnosed hyperuricemia (UA >7 mg/dL) and no baseline diabetes, cardiovascular disease, or metabolic disorders. Patients initiating ULT were propensity score-matched (1:1) to untreated controls (2,906 pairs). The primary outcome was a composite cardiometabolic endpoint. Results: Over a median follow-up of 3.03 years, ULT initiation was associated with increased risk of the composite cardiometabolic outcome (HR 1.18, 95% CI 1.07-1.30) and of all-cause mortality (HR 1.52, 95% CI 1.27-1.82). The increased risk was evident among men, individuals without prior gout, users of xanthine oxidase inhibitors, and those who achieved target serum urate (<5 mg/dL) within 6 months. Conclusions: In individuals without major cardiometabolic disease, initiating ULT was associated with increased cardiometabolic risk. Serum urate may have context-dependent physiological roles in early metabolic states, warranting further research.