• Natalie McCormick, Chio Yokose, Jie Wei, Na Lu, Deborah J Wexler, J Antonio Aviña-Zubieta, Mary A De Vera, Yuqing Zhang, and Hyon K Choi.
• Clinical Epidemiology Program, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, Massachusetts; The Mongan Institute, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts; and Arthritis Research Canada, Vancouver, British Columbia, Canada (N.M., H.K.C.).
• Ann. Intern. Med. 2023 Aug 1; 176 (8): 106710801067-1080.

BackgroundSodium-glucose cotransporter-2 inhibitors (SGLT2is) decrease serum urate levels, but whether this translates into prevention of recurrent flares among patients with gout and gout-primary emergency department (ED) visits or hospitalizations is unknown.ObjectiveTo compare gout flares and cardiovascular events among patients with gout initiating SGLT2is versus dipeptidyl peptidase 4 inhibitors (DPP-4is), another second-line glucose-lowering agent not associated with serum urate levels or cardiovascular risk.DesignPropensity score-matched, new-user cohort study.SettingGeneral population database from 1 January 2014 to 30 June 2022.ParticipantsPatients with gout and type 2 diabetes.MeasurementsThe primary outcome was recurrent gout flare counts ascertained by ED, hospitalization, outpatient, and medication dispensing records. Secondary outcomes included myocardial infarction and stroke; genital infection (positive control) and osteoarthritis encounter (negative control) were also assessed. Poisson and Cox proportional hazards regressions were used with 1:1 propensity score matching (primary analysis) and overlap weighting (sensitivity analysis).ResultsAfter propensity score matching, the flare rate was lower among SGLT2i initiators than DPP-4i initiators (52.4 and 79.7 events per 1000 person-years, respectively), with a rate ratio (RR) of 0.66 (95% CI, 0.57 to 0.75) and a rate difference (RD) of -27.4 (CI, -36.0 to -18.7) per 1000 person-years. The corresponding RR and RD for gout-primary ED visits and hospitalizations were 0.52 (CI, 0.32 to 0.84) and -3.4 (CI, -5.8 to -0.9) per 1000 person-years, respectively. The corresponding hazard ratio (HR) and RD for myocardial infarction were 0.69 (CI, 0.54 to 0.88) and -7.6 (CI, -12.4 to -2.8) per 1000 person-years; the HR for stroke was 0.81 (CI, 0.62 to 1.05). Those who initiated SGLT2is showed higher risk for genital infection (HR, 2.15 [CI, 1.39 to 3.30]) and no altered risk for osteoarthritis encounter (HR, 1.07 [CI, 0.95 to 1.20]). Results were similar when propensity score overlap weighting was applied.LimitationParticipants had concurrent type 2 diabetes.ConclusionAmong patients with gout, SGLT2is may reduce recurrent flares and gout-primary ED visits and hospitalizations and may provide cardiovascular benefits.Primary Funding SourceNational Institute of Arthritis and Musculoskeletal and Skin Diseases.

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