Hyperuricemia (HUA) has become a common metabolic disease in China. Although obesity is an established independent risk factor for HUA, previous studies have mainly focused on static body weight indicators. Evidence on the impact of dynamic body weight changes on HUA risk and its population heterogeneity remains limited.

To explore the association between dynamic body weight changes and the risk of new-onset hyperuricemia in adults undergoing health examinations, providing a scientific basis for formulating personalized prevention strategies.

A total of 18 179 adult participants who underwent health examinations at least twice between January 2015 and May 2025 at the Health Management Center, the First Affiliated Hospital of Hainan Medical University were enrolled. Baseline was defined as the first examination, and the follow-up endpoint was new-onset HUA or the last follow-up. Body weight change was defined as the percentage change from baseline to follow-up endpoint and categorized into five groups: significant weight loss (body weight change≤-5.0%), modest weight loss (-5.0%< body weight change≤-1.0%), stable weight (-1.0%< body weight change <1.0%), modest weight gain (1.0%≤body weight change <5.0%), and significant weight gain (body weight change≥5.0%). Demographic characteristics, physical examination indicators, and laboratory test results were collected. Univariate and multivariate Logistic regression models were employed to analyze the association between body weight change and new-onset HUA. A restricted cubic spline (RCS) model was applied to fit the dose-response relationship between body weight change percentage and HUA risk. Subgroup analyses and interaction tests were performed by sex, age, and baseline BMI. Furthermore, joint effect analysis was conducted to clarify the combined influence of sex, age, baseline BMI, and body weight change on HUA risk.

During a total follow-up of 52 016 person-years, with a mean follow-up of (2.88±2.11) years, 2 686 new HUA cases were identified, with an incidence density of 51.64 per 1 000 person-years. Multivariate Logistic regression models showed that, compared with the stable weight group, significant weight loss was associated with a 38.2% lower risk of HUA (OR=0.618, 95%CI=0.489-0.782, P<0.01), while significant weight gain was associated with a 42.8% higher risk (OR=1.428, 95%CI=1.192-1.711, P<0.01). No evidence of a nonlinear association between percentage body weight change and HUA risk was observed (P_nonlinear=0.631). Significant interactions existed between body weight change and sex, age, and baseline BMI (P<0.01). Joint effect analysis further confirmed that the protective effect of substantial body weight loss on HUA was more prominent in females (OR=0.167, 95%CI=0.105-0.266), non-overweight/non-obese individuals (baseline BMI<24.0 kg/m²)(OR=0.569, 95%CI=0.377-0.860) and people aged 18-<40 years (OR=0.418, 95%CI=0.263-0.663)(P<0.05).

Significant body weight gain is associated with increased HUA risk, while significant body weight loss is associated with decreased risk. This association exhibits heterogeneity by sex, age, and baseline BMI. Differentiated weight management strategies tailored to different populations should be implemented to effectively reduce HUA incidence.