Efficacy and Safety of Pemafibrate Versus Bezafibrate to Treat Patients with Hypertriglyceridemia: A Randomized Crossover Study

Aim: Pemafibrate is a highly selective agonist for peroxisome proliferator-activated receptor (PPAR)-α, a key regulator of lipid and glucose metabolism. We compared the efficacy and safety of pemafibrate with those of bezafibrate, a nonselective PPAR-α agonist. Methods: In this randomized crossover study, 60 patients with hypertriglyceridemia (fasting triglyceride [TG] ≥ 150 mg/dL) were treated with pemafibrate of 0.2 mg/day or bezafibrate of 400 mg/day for 24 weeks. The primary endpoint was percent change (%Change) from baseline in TG levels, while the secondary endpoints were %Change in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (Apo A-I) levels. Results: The %Change in TG and Apo A-I levels was significantly greater with pemafibrate than with bezafibrate (−46.1% vs. −34.7%,p＜0.001; 9.2% vs. 5.7%,p =0.018, respectively). %Change in HDL-C levels was not significantly different between the two treatments. %Change in liver enzyme levels was markedly decreased with pemafibrate than with bezafibrate. Creatinine levels significantly increased in both treatments; however, its %Change was significantly lower with pemafibrate than with bezafibrate (5.72% vs. 15.5%,p＜0.001). The incidence of adverse events (AEs) or serious AEs did not differ between the two treatments; however, the number of patients with elevated creatinine levels (≥ 0.5 mg/dL and/or 25% from baseline) was significantly lower in the bezafibrate group than in the pemafibrate group (16/60 vs. 3/60,p =0.004). Conclusion: Compared with bezafibrate, pemafibrate is more effective in decreasing TG levels and increasing Apo A-I levels and is safer regarding liver and renal function.