Association between uric acid levels and cardio‐renal outcomes and death in patients with type 2 diabetes: A subanalysis of EMPA‐REG OUTCOME

In the EMPA‐REG OUTCOME trial, we explored the association between pre‐randomization uric acid level tertile (<309.30 μmol/L; 309.30 to <387.21 μmol/L; ≥387.21 μmol/L) and cardiovascular (CV) death, hospitalization for heart failure (HHF), HHF or CV death, all‐cause mortality, three‐point major adverse CV events (MACE), and incident or worsening nephropathy. Patients with type 2 diabetes and CV disease received empagliflozin or placebo. The median baseline plasma uric acid level was 344.98 μmol/L, and patients’ baseline characteristics were mainly balanced across tertiles. Baseline uric acid levels were associated with cardio‐renal outcomes: in the placebo group, for the highest versus lowest tertile, the multivariable hazard ratios for three‐point MACE, HHF or CV death, and incident or worsening nephropathy were 1.22 (95% confidence interval [CI] 0.89–1.67; P = 0.2088), 1.51 (95% CI 1.02–2.23; P = 0.0396) and 1.77 (95% CI 1.33–2.34; P < 0.0001), respectively. When tested as a continuous variable, baseline uric acid was associated with all outcomes in the placebo group. Empagliflozin improved all cardio‐renal outcomes across tertiles, with all interaction P values >0.05. Further investigation of these relationships is required.