OP0156 INITIATION OF SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS AND RECURRENT GOUT FLARES IN GOUT PATIENTS WITH TYPE 2 DIABETES: A GENERAL POPULATION-BASED COHORT STUDY

Abstract

BackgroundGout flares may increase risk of cardiovascular events.[1]Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are associated with lower risk of incident gout (primary prevention); however, their role in recurrent flares among gout patients (secondary prevention), and their cardiovascular risk remains unknown.ObjectivesTo assess rate of recurrent gout flares in prevalent gout patients with type 2 diabetes initiating SGLT2i versus dipeptidyl peptidase-4 inhibitors (DPP4i), two second-line glucose-lowering agents for type 2 diabetes.MethodsThis new-user, active comparator cohort study used administrative health data covering nearly all residents of British Columbia, Canada from Jan 2014 to June 2022, including all dispensed prescriptions, regardless of funder. Primary outcome was recurrent gout flare counts, ascertained by emergency department (ED), hospitalization, outpatient, and medication dispensing records.[1]We also restricted to flares requiring hospitalization or ED visit, and stratified by sex, age, gout intensity (presence of ≥1 gout-coded encounter or colchicine dispensing over past year) and diuretic and urate-lowering therapy (ULT) use. Myocardial infarction and stroke were secondary outcomes. We also assessed genital infection as positive control and osteoarthritis as negative control. Poisson and Cox proportional hazards models were used with 1:1 propensity matching.ResultsWe included 8150 gout patients with type 2 diabetes (mean age 66, 71% male, 59% with cardiovascular disease). Flare rate was lower among SGLT2i initiators (52.4 events per 1000 person-years) than DPP4i initiators (79.7 events per 1000 person-years): rate ratio (RR) 0.66 (95% CI: 0.57, 0.75) and rate difference (RD) -27.4 (-36.0, -18.7). RR and RD for flares requiring hospitalization or ED visit were 0.52 (0.32, 0.84) and -3.4 (-5.8, -0.9), respectively.Results were consistent regardless of sex or age (Table 1). RR was also consistent regardless of baseline gout intensity or diuretic or ULT use, though absolute RD was higher in patients with greater gout intensity: -71.6 [-111.1, -32.1] vs. 20.8 [-28.8, -12.7] per 1000 person-years, respectively.Hazard ratio (HR) and RD were 0.69 (0.54, 0.88) and -7.6 (-12.4, -2.8) per 1000 person-years for myocardial infarction; HR, 0.81 (0.62, 1.05) for stroke. For control outcomes, SGLT2i initiators had higher risk of genital infection, while there was no difference in risk of osteoarthritis (Table 1).ConclusionFor gout patients, SGLT2i may offer pleiotropic cardiovascular and recurrent flare frequency benefits.Reference[1] Cipolletta et al.JAMA2022Table 1.Recurrent gout flare count and cardiovascular and control outcomes among gout patients with type 2 diabetes, after propensity-score matchingSGLT2i compared with DPP4i [Reference]Gout Flare CountRate Ratio (95% CI)Rate Difference (95% CI)Overall (Primary outcome)0.66 (0.57, 0.75)-27.4 (-36.0, -18.7)Flares requiring hospitalization or emergency visits0.52 (0.32, 0.84)-3.4 (-5.8, -0.9)SubgroupsSexMen0.63 (0.54, 0.73)-33.6 (-44.3, -22.8)Women0.43 (0.29, 0.62)-35.0 (-48.9, -21.0)Age≤ 65 years0.69 (0.56, 0.85)-22.9 (-35.8. -10.0)> 65 years0.51 (0.42, 0.62)-45.3 (-58.0, -32.6)Baseline diuretic useYes0.75 (0.62, 0.92)-24.8 (-42.1, -7.5)No0.63 (0.52, 0.77)-24.1 (-34.2, -14.1)Baseline urate-lowering therapy useYes0.66 (0.50, 0.87)-25.2 (-41.8, -8.6)No0.56 (0.48, 0.66)-39.5 (-50.4, -28.7)Baseline gout intensityHigher0.65 (0.51, 0.82)-71.6 (-111.1, -32.1)Lower0.64 (0.53, 0.76)-20.8 (-28.8, -12.7)Cardiovascular OutcomesHazard Ratio (95% CI)Risk Difference (95% CI)Myocardial infarction0.69 (0.54, 0.88)-7.6 (-12.4, -2.8)Stroke0.81 (0.62, 1.05)-3.9 (-8.3, 0.4)Control OutcomesHazard Ratio (95% CI)Risk Difference (95% CI)Genital infection (POSITIVE)2.15 (1.39, 3.30)5.0 (2.2, 7.9)Osteoarthritis (NEGATIVE)1.07 (0.95, 1.20)4.4 (-6.8, 15.7)SGLT2i, sodium glucose cotransporter-2 inhibitors; DPP4i, dipeptidyl peptidase 4 inhibitorsAcknowledgements:NIL.Disclosure of InterestsNatalie McCormick: None declared, Chio Yokose: None declared, Jie Wei: None declared, Leo Lu: None declared, Deborah Wexler Consultant of: Served on Data Monitoring Committees for Novo Nordisk, J. Antonio Aviña-Zubieta: None declared, Mary De Vera: None declared, Yuqing Zhang: None declared, Hyon Choi Consultant of: Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart., Grant/research support from: Ironwood and Horizon.