OBJECTIVES: Obesity affects 53% of gout patients, while its effect on urate-lowering therapy (ULT) is unclear. This study aimed to compare the response to febuxostat among different body mass index (BMI) catalogs of male gout patients. METHODS: A prospective study recruited 633 men with gout, classified by BMI into normal-weight, overweight, and obese groups. Baseline age, disease duration, and serum urate (SU) levels were matched simultaneously. All participants received febuxostat for 12 weeks, increasing the dosage from 20 to 40 mg daily. We compared the efficacy of ULT and the incidence of gout flares in three groups. Cox regression analysis was used to identify risk factors for achieving target SU levels before and after matching. Restricted cubic spline (RCS) curves were used to illustrate the relationship between BMI and hazard ratio (HR) for SU achievement. RESULTS: The proportion of participants achieving SU <
6.0 mg/dl in the obese group was 38.9%, significantly lower than the overweight (54.2%) and normal-weight groups (63.8%) (p <
0.05), with no significant difference between the overweight and normal-weight groups at week 12. High BMI (HR = 0.92, 95% CI 0.89-0.96, p <
0.001) independently prevented achieving the SU target, with a similar effect after matching. Obese and overweight individuals had a higher cumulative incidence of gout flares compared with the normal-weight group (p <
0.05). The linear relationship between BMI and HR for achieving the SU target was suggested by RCS (nonlinear p >
0.05). CONCLUSION: Obesity significantly reduces the efficacy of febuxostat-based ULT in male gout patients rather than being overweight.This study was registered in the China Clinical Trial Registry (#ChiCTR2300078804).