Empagliflozin and uric acid metabolism in diabetes: A post hoc analysis of the EMPA‐REG OUTCOME trial
Abstract
Aim: To evaluate the effect of empagliflozin on uric acid (UA) levels, antigout medication and gout episodes in the EMPA-REG OUTCOME trial (NCT01131676). Materials and methods: A total of 7020 patients with type 2 diabetes (T2D) were randomized to either empagliflozin (10 or 25 mg) or placebo. The effects of empagliflozin versus placebo on UA concentration were assessed using mixed linear models. A composite outcome of new prescription of antigout medication or gout episode was studied with Cox proportional hazards models. Results: Empagliflozin reduced serum UA levels versus placebo: week 52 adjusted mean treatment difference = À0.37 (95% confidence interval [CI] À0.42, À0.31) mg/dL; this was more pronounced in patients with baseline UA ≥ 7.0 mg/dL versus <7.0 mg/dL: week 52 adjusted mean treatment difference = À0.56 (95% CI À0.68, À0.43) and À0.30 (95% CI À0.37, À0.24) mg/dL, respectively. Among 6607 patients not taking antigout medications at baseline, 5.2% had a gout episode or initiated antigout treatment versus 3.6% in the placebo and empagliflozin groups, respectively: hazard ratio 0.67 (95% CI 0.53, 0.85; P = 0.001). Both components of the composite outcome contributed to the reduction with empagliflozin in the composite. Risk reduction was similar with both empagliflozin doses. Conclusions: Empagliflozin reduced UA levels and the composite of gout episodes or prescription of antigout medication. These clinically important findings expand the utility of empagliflozin as a potential antigout treatment in patients with T2D, beyond its well-established cardio-renal benefits.
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