Impact of fenofibrate therapy on serum uric acid concentrations: a review and meta-analysis

Abstract

Fenofibrate is a marketed fibric acid derivative for lipid-lowering in patients with lipid disorders. Numerous studies have proven fenofibrate had a certain effect on serum uric acid, here we conducted this study to quantitatively assess the effect of fenofibrate intervention in modulating serum uric acid concentration and the influence on serum creatinine. The PubMed, Embase and Cochrane were systematically searched for randomized controlled trials update to January, 2020. Primary endpoints focused on serum uric acid concentration and serum creatinine concentration. The pooled effects were calculated as weighted mean difference (WMD) by a random-effects model. Finally, 9 studies representing 487 patients were included in the meta-analysis. The meta-analysis demonstrated that fenofibrate significantly reduced serum uric acid levels (WMD -1.32 mg/dL, 95%CI -1.61 to -1.03, p < 0.001) and an elevated level in serum creatinine (WMD 0.09 mg/dL, 95%CI 0.02 to 0.15, p < 0.001) following fenofibrate therapy compared with placebo. The present study provided strong evidence that fenofibrate intervention exerted a significant reduction on serum uric acid and a mild increase on serum creatinine. Metaanalysis suggested that there were no significant association between the serum uric acid lowering effect with either dose or treatment duration. Overall, our meta-analysis ascertained that fenofibrate have potential therapeutic effects in patients with lipid metabolic abnormalities but with mid nephrotoxicity. There is strong evidence to provide future direction of practical application and clinical researches of fenofibrate.

Effects of a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator, Pemafibrate, on Metabolic Parameters: A Retrospective Longitudinal Study

“…One of fibrates, fenofibrate, decreased serum UA levels by increasing its urinary excretion, most likely through the inhibition of URAT1 by fenofibric acid, its major metabolite [ 57 ]. The meta-analyses showed a significant reduction in plasma UA concentrations following fenofibrate therapy [ 58 , 59 ]. However, reduction of serum UA by pemafibrate was not reported.…”

Efficacy and safety of pemafibrate in patients with chronic kidney disease: A retrospective study

“…Moreover, Feno-F significantly reduced serum UA and further lowered plasma TG levels. [7] However, a few reports suggested that conventional fibrates may be associated with the risk of increased sCr levels. [9,10] In the present study, we confirmed that both Beza-F and Feno-F induced eGFR reduction even when administered at low doses.…”

“…In addition to lowering plasma TG levels, Feno-F significantly reduced serum uric acid (UA). [7] Moreover, treatment with Feno-F significantly improved arterial endothelial function. [8] Furthermore, a few studies have reported an increase in serum creatinine (sCr) during fibrate therapy.…”

The effect of empagliflozin and fenofibrate therapies, alone and in combination, on the serum urate concentration in hyperuricaemic type 2 diabetes

“…The mean 0.07 mmol/L serum urate reduction after 1 week of fenofibrate in our participants was close to the 0.06 mmol/L mean decrease after 6 weeks of treatment in a large clinical trial in type 2 diabetes 10 and the 0.08 mmol/L reduction in a metanalysis. 3 when there is hypertriglyceridaemia and/or retinopathy, 11 would thus have the added benefit of lowering serum urate. The pharmacodynamic effects of allopurinol are complex, but the dose required to achieve a serum urate of less than 0.36 mmol/L from the mean baseline level in our participants (0.43 mmol/L) is 125 mg daily.…”