Aim: Fenofibrate lowers serum uric acid (UA) levels in small short-term trials and gout events in small case series. We assessed the long-term effect of fenofibrate treatment on UA and gout events in patients with type 2 diabetes (T2D).

Methods: T2D patients (n=9795) were randomised to once daily co-micronised fenofibrate 200mg (n=4,895) or matching placebo (n=4,900) for an average of 5-years follow-up. Serum UA was measured at baseline and following 6-weeks active fenofibrate run-in pre-randomisation. UA was quantified again at 2-years in a subset of 1955 participants. Hospitalisations for or with reported gout (adjudicated by 2 physicians masked to treatment allocation), and all other reported gout attacks, were recorded at 6 monthly clinic visits for analysis.

Results: With placebo allocation, first gout event rates over 5 years were >2% when UA exceeded 0.36mmmol/L at baseline, and >10% when UA exceeded 0.42mmol/L. UA levels fell by 20% with 6-weeks fenofibrate during the run-in phase (p<0.001 paired t-test). At 2 years, compared to baseline, UA was 17.8% lower in the fenofibrate group and 2.2% higher in the placebo group (between group difference 20%; p<0.001). There were 81 (1.7%) first on-study gout events in the fenofibrate group compared to 151 (3.1%) in the placebo group (HR 0.54; 95%CI 0.41-0.70: p<0.001). Similar estimated risk reductions were seen among men, women, those with dyslipidaemia, those on diuretics and those with UA>0.36 or >0.42mmol/L at baseline. There was no heterogeneity of treatment effect for participants taking or not taking allopurinol amongst those with baseline UA>0.36 or >0.42mmol/L.

Conclusions: Gout events occurred mainly with higher baseline UA levels. Fenofibrate lowered UA levels by 20% on average, and almost halved on-study first gout events and hospitalisations with long-term treatment over 5 years. Fenofibrate may be a useful adjunct for treatment of individuals with diabetes and elevated UA.