Effects of Empagliflozin on Serum Uric Acid and Gout in CKD

Background: Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce serum uric acid and may reduce the risk of gout in patients with diabetes and/or heart failure, but randomized evidence in patients with CKD is lacking. Methods: EMPA-KIDNEY compared empagliflozin 10 mg daily with placebo in 6609 patients with CKD (Clinicaltrials.gov: NCT03594110). Eligible patients had an eGFR of 20 to <45; or 45 to <90 mL/min/1.73m2 with ≥200 mg/g albuminuria. Serum uric acid measured at randomization, 2 and 18 months was analyzed using a mixed model repeated measures approach including interaction terms to estimate subgroup-specific effects with calculation of heterogeneity or trend statistics. In exploratory analyses, first and total gout events were analyzed in Cox regression models with the Andersen-Gill extension for total events. All models were adjusted for age, sex, region, eGFR, uACR and diabetes status. Results: Mean±SD baseline serum uric acid was 431.3±113.5 µmol/L. Empagliflozin reduced serum uric acid (study average between-group difference [95% CI] -25.6 [-30.3, -21.0] µmol/L). Uric acid lowering was greater in participants without diabetes (heterogeneity P<0.001) and at higher eGFR (trend P<0.001; Figure). During 2 years’ median follow-up, there was no significant effect of empagliflozin on risk of gout events alone (whether analyzing first or all occurrences, Table) which was consistent across subgroups including by baseline diabetes, eGFR and uric acid concentration (heterogeneity P all >0.1). Conclusion: In EMPA-KIDNEY, empagliflozin modestly reduced serum uric acid with greater effects at higher eGFR and in those without diabetes, but did not significantly reduce episodes of gout. Funding: Commercial Support - EMPA-KIDNEY trial funding from Boehringer Ingelheim & Eli LillyEffects of empagliflozin versus placebo on serum uric acid and gout in subgroups defined by baseline characteristics Effects of empagliflozin versus placebo on gout - Empagliflozin n/N Empagliflozin Rateper 1000patient-years Placebon/N Placebo Rateper 1000patient-years Hazard Ratio(95% CI) First occurrence of gout 278/3304 45.7 317/3305 52.3 0.87 (0.74-1.02) All occurrences of gout 404/3304 62.2 465/3305 71.7 0.86 (0.72-1.03) First occurrence of gout or new initiation of xanthine oxidase inhibitor, primary uricosuric agent or colchicine in participants not on such therapy at randomization 261/2135 66.3 314/2124 81.8 0.81 (0.69-0.96)