Fenofibrate reduces gout risk in T2D

Patients with type 2 diabetes (T2D) experienced reductions in plasma uric acid concentrations and subsequently, fewer gout events following treatment with fenofibrate, according to a post hoc analysis of the FIELD* trial.

Patients with type 2 diabetes (T2D) experienced reductions in plasma uric acid concentrations and subsequently, fewer gout events following treatment with fenofibrate, according to a post hoc analysis of the FIELD* trial.
“The most clinically relevant and important finding from these post hoc analyses was that fenofibrate therapy almost halved the rate of incident episodes of acute gout. These findings reflect the fundamental importance of uric acid in the risk of future gout events,” said the researchers.
“Fenofibrate, which has existing indications in T2D for lipid management … could be a valuable adjunct to reduce the burden of gout in individuals with T2D,” they said.
A total of 9,795 participants aged 50–75 years (mean age 62 years, 37 percent female, mean BMI 29.8 kg/m²) with T2D from 63 centres in Australia, New Zealand, and Finland were randomized to receive co-micronized fenofibrate (200 mg QD; n=4,895) or placebo (n=4,900) for a median 5 years. Gout history was determined through gout medication prescription, with 7 percent of patients on allopurinol and <1 percent each on either colchicine or probenecid.
Prior to randomization, all patients received fenofibrate for a 6-week period, during which patients experienced a 20.2 percent reduction (-0.06 mmol/L) in uric acid levels. [Lancet Diabetes Endocrinol 2018;6:310-318]
Patients who received fenofibrate had a reduced risk of experiencing at least one first gout event over the 5-year period compared with those who received placebo (2 percent vs 3 percent, hazard ratio [HR], 0.54, 95 percent confidence interval [CI], 0.41–0.70; p<0.0001), as well as a reduced risk of all recurrent gout events (HR, 0.48, 95 percent CI, 0.37–0.60; p<0.0001).
The incidence of first gout events was lower among patients on fenofibrate vs placebo regardless of hyperuricaemia threshold (3.4 percent vs 7.7 percent in patients with baseline uric acid levels >0.36 mmol/L and 5.7 percent vs 13.9 percent in patients with baseline uric acid levels >0.42 mmol/L).
Fewer patients on fenofibrate initiated new gout medication during the trial compared with those on placebo (2 percent vs 3 percent, adjusted odds ratio, 0.55; p<0.0001) and the rate of discontinuation was comparable between patients on fenofibrate and placebo (11 percent vs 10 percent).
A random subset analysis of 2,000 patients showed that at 1 year, patients in the fenofibrate arm sustained the pre-randomization reduction in uric acid levels with a 20.1 percent lower uric acid level compared with patients assigned to placebo (between-group difference, 20 percent; p<0.0001). This reduction in uric acid levels was smaller among patients already on allopurinol (10.3 percent vs 20.8 percent; p<0.0007). 
According to the researchers, the smaller impact of fenofibrate in patients on allopurinol suggests that fenofibrate may act by increasing the excretion of oxypurinol, an active metabolite of allopurinol, an action similar to that of other uricosuric drugs with “gout-specific indications”. [J Rheumatol 2001;28:2294-2297] However, an increased risk of uric acid renal stones, a potential adverse effect of uricosuric drugs, was not seen in patients on fenofibrate, suggesting that fenofibrate may also increase urinary pH, they said.
“[The study] adds substantially to the growing body of evidence supporting the pre-emptive and aggressive management of gout in patients with diabetes, who could go on to face the debilitating consequences of both conditions. The health economic ramifications for any agent that can be used safely to exert dual actions on end-organ manifestations are extensive,” highlighted Assistant Professor Puja Khanna from the University of Michigan in Ann Arbor, Michigan, US, in a commentary. [Lancet Diabetes Endocrinol 2018;6:263-264]
 
*FIELD: Fenofibrate Intervention and Event Lowering in Diabetes