Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2016

Fenofibrate Reduces Uric Acid Levels and Gout Events in Type 2 Diabetes: Results from the Field Study (#63)

Boris Waldman 1 2 , Jean-Claude Ansquer 3 , David Sullivan 1 2 , Alicia Jenkins 1 , Neil McGill 2 , Luke Buizen 1 , Michael Feher 4 5 , Christelle Foucher 3 , Antero Kesaniemi 6 , Jeffrey Flack 7 , Michael D'Emden 8 , John Hedley 9 , Tony Keech 1 2
  1. NHMRC Clinical Trials Centre, Camperdown, NSW, Australia
  2. Royal Prince Alfred Hospital, Sydney, NSW, Australia
  3. Clinsciences, Dijon, France
  4. Chelsea and Westminster Hospital, London, United Kingdom
  5. Chelsea and Westminster Hospital, London, United Kingdom
  6. University of Oulu, Oulu, Finland
  7. University of New South Wales, Sydney, NSW, Australia
  8. University of Queensland, Brisbane, Australia
  9. Wairau Hospital, Blenheim, New Zealand

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.