Background/Purpose: Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) are currently indicated as second-line therapy for type 2 diabetes and are also approved for the treatment of heart failure and chronic kidney disease, all comorbidities prevalent among gout patients. SGLT2i have also been found to reduce serum urate (SU), the causal mediator of gout, by up to 1.8 mg/dL among those with hyperuricemia (Doehner et al., Eur Heart J, 2022). However, no data are available specifically among patients with gout. We sought to determine the SU change among gout patients treated with SGLT2i or sulfonylurea (SFU, another second-line diabetes agent).

Methods: Using the Mass General Brigham electronic health record database, we identified all gout patients initiating SGLT2i or SFU who had SU measured within 3 months before and after the initiation through 2/2/2023. Gout patients were identified using an algorithm with a positive predictive value of 0.9 against the 2015 ACR/EULAR gout criteria and were required to have baseline SU ≥6 mg/dL. A rheumatologist reviewed all identified patient records to confirm their gout diagnosis and the initiation and continuation of SGLT2i or SFU treatment during the study period (up to 6 months). Patients who had SU measured < 7 days after the initial prescription or in the setting of an acute gout flare were excluded, as were patients who initiated or changed the dose of urate-lowering therapy (ULT) just prior to or during the study period. We first calculated the within-group SU change. Then, we compared the two groups for SU change using multivariable linear regression adjusting for age, sex, baseline SU, and ULT use. We additionally adjusted for each of the other covariates for robustness and conducted subgroup analyses per ULT use and key comorbidities.

Results: There were 23 patients with gout who initiated SGLT2i and 24 patients who initiated SFU. The SGLT2i-initiators were slightly older, while the SFU-initiators included more females and had higher baseline SU (Table 1). Among SGLT2i-initiators, the mean SU change was -1.6 mg/dL (95% CI, -2.2 to -0.9), compared with 0.3 mg/dL (95% CI, -0.5 to 1.0) among SFU-initiators (Figure 1). During the study period, 43.5% of SGLT2i-initiators reached target SU < 6 mg/dL compared to 4.2% of SFU-initiators. The adjusted SU change associated with SGLT2i initiation was -1.6 mg/dL (95% CI, -2.6 to -0.7) compared with SFU initiation, and remained similar when stratified by ULT use (Table 2). These results did not change materially with additional adjustments for other covariates but were slightly attenuated but still significant among those with diabetes.

Conclusion: In this comparative effectiveness analysis of gout patients, SGLT2i use was associated with a notable reduction in SU over several months, whereas SFU use was not. With their proven multiple cardiometabolic-kidney benefits, these results suggest that SGLT2i could be a much-needed multi-purpose medication for the synergistic treatment of gout and its comorbidities, regardless of ULT use, and call for randomized clinical trials to test this hypothesis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-urate-change-among-gout-patients-initiating-sodium-glucose-cotransporter-type-2-inhibitors-sglt2i-vs-sulfonylureas-a-comparative-effectiveness-analysis/