Background/Purpose: Obesity affects >50% of individuals with gout and is the most important modifiable risk factor for gout. Thus, novel anti-obesity medications (AOM, e.g., semaglutide and tirzepatide), which have revolutionized the medical management of obesity and associated cardiovascular-kidney-metabolic (CKM) comorbidities, are highly relevant for patients with gout. Researchers have associated weight loss through bariatric surgery or lifestyle changes with reduced serum urate (SU), but no study has examined how novel AOM affects SU. We sought to determine the SU change among patients with gout and baseline hyperuricemia treated with novel AOM.

Methods: Using the Mass General Brigham electronic health record (EHR) database, we identified all patients with gout with baseline hyperuricemia (SU ≥6 mg/dL) who had SU measurements available within 3 months before and >3 months after starting a novel AOM as part of routine clinical care. We defined novel AOM as semaglutide or tirzepatide. We identified patients with gout using an algorithm with a positive predictive value of 0.9 against the 2015 ACR/EULAR gout classification criteria. A rheumatologist and a trained research team member manually reviewed all charts and adjudicated any discrepant findings by consensus. We excluded patients who had SU measured in the setting of an acute gout flare and patients who started or changed the dose of urate-lowering therapy during the study period. We calculated the weight change for all individuals using measurements available in the EHR on dates closest to the SU measurements and grouped them into three categories (< 5%, 5-10%, or >10%). We used linear general estimating equations with robust variance to evaluate the association of baseline weight and weight change (either in absolute or categorical) with serum urate.

Results: Our study included 22 patients with gout who were started on a novel AOM. The mean age was 54.6 years, and the majority were male (77.3%) (Table 1). Mean BMI was 39.3 kg/m2 at baseline. The primary indication for novel AOM treatment was obesity in 11 patients and type 2 diabetes (T2DM) in 11 patients, though many of those with T2DM also had comorbid obesity. Mean treatment duration was 258 days. There were 45.5%, 31.8%, and 22.7% of patients who lost < 5%, 5-10%, and >10% body weight, respectively. There was a significant association between weight and SU change (Table 2, Figure 1). Each kg of weight loss was associated with a 0.13 mg/dL reduction in SU, while each BMI unit reduction was associated with a 0.41 mg/dL reduction in SU. Compared to those who lost < 5% of their body weight, those who lost 5-10% of their body weight had a 0.73 mg/dL greater reduction in SU, and those who lost >10% of their body weight had a 2.36 mg/dL greater reduction in SU (p for trend < 0.001) (Table 2).

Conclusion: In this retrospective study, novel AOM-induced weight loss was associated with a significant reduction in SU among patients with gout with baseline hyperuricemia. These results suggest that novel AOM may be a powerful multi-purpose medication for the many patients with gout and obesity and call for larger-scale studies to test this hypothesis.

Table 1. Baseline Characteristics of Patients with Gout Treated with Novel AOM

Table 2. Association Between Weight and Serum Urate Change Among Patients with Gout Treated with Novel AOM

Figure 1. Body Weight Change and Serum Urate Change Among Patients with Gout and Baseline Hyperuricemia

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/novel-anti-obesity-medications-and-serum-urate-change-among-patients-with-gout-and-baseline-hyperuricemia/