Effect of fenofibrate on uric acid and gout in type 2 diabetes: a post-hoc analysis of the randomised, controlled FIELD study

Background Gout is a painful disorder and is common in type 2 diabetes. Fenofibrate lowers uric acid and reduces gout attacks in small, short-term studies. Whether fenofibrate produces sustained reductions in uric acid and gout attacks is unknown. Methods In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial, participants aged 50-75 years with type 2 diabetes were randomly assigned to receive either co-micronised fenofibrate 200 mg once per day or matching placebo for a median of 5 years follow-up. We did a post-hoc analysis of recorded on-study gout attacks and plasma uric acid concentrations according to treatment allocation. The outcomes of this analysis were change in uric acid concentrations and risk of on-study gout attacks. The FIELD study is registered with ISRCTN, number ISRCTN64783481. Findings Between Feb 23, 1998, and Nov 3, 2000, 9795 patients were randomly assigned to fenofibrate (n= 4895) or placebo (n= 4900) in the FIELD study. Uric acid concentrations fell by 20.2% (95% CI 19.9-20.5) during the 6-week active fenofibrate run-in period immediately pre-randomisation (a reduction of 0.06 mmol/ L or 1 mg/ dL) and remained -20.1% (18.5-21.7, p< 0.0001) lower in patients taking fenofibrate than in those on placebo in a random subset re-measured at 1 year. With placebo allocation, there were 151 (3%) first gout events over 5 years, compared with 81 (2%) among those allocated fenofibrate (HR with treatment 0.54, 95% CI 0.41-0.70; p< 0.0001). In the placebo group, the cumulative proportion of patients with first gout events was 7.7% in patients with baseline uric acid concentration higher than 0.36 mmol/ L and 13.9% in those with baseline uric acid concentration higher than 0.42 mmol/ L, compared with 3.4% and 5.7%, respectively, in the fenofibrate group. Risk reductions were similar among men and women and those with dyslipidaemia, on diuretics, and with elevated uric acid concentrations. For participants with elevated baseline uric acid concentrations despite taking allopurinol at study entry, there was no heterogeneity of the treatment effect of fenofibrate on gout risk. Taking account of all gout events, fenofibrate treatment halved the risk (HR 0.48, 95% CI 0.37-0.60; p< 0.0001) compared with placebo. Interpretation Fenofibrate lowered uric acid concentrations by 20%, and almost halved first on-study gout events over 5 years of treatment. Fenofibrate could be a useful adjunct for preventing gout in diabetes.