Impact of pemafibrate on lipid profile and insulin resistance in patients with statin-treated coronary artery disease with metabolic syndrome

Abstract Background Pemafibrate is a highly selective agonist for peroxisome proliferator-activated receptor α, a vital modulator of lipid and glucose metabolism. We examined the effects of this drug on lipid markers and insulin resistance in patients with metabolic syndrome (MetS). Methods In the randomized, crossover PEBE 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, followed by crossover of another 24-weeks. Forty-six of 60 patients (77%) enrolled in the PEBE study were founded to have MetS. In the present subanalysis, we compared patients with MetS (MetS group, n = 46) and those without MetS (Non-MetS group, n =14). The primary endpoints were changes from baseline in serum TG, high-density lipoprotein cholesterol (HDL-C), and apolipoprotein A-I (Apo A-I) levels, while the secondary endpoint was change in the homeostasis model assessment of insulin resistance (HOMA-IR). Results There was a significant decrease in serum TG levels (from 266.6 mg/dL to 148.0 mg/dL in MetS group, p < 0.001; from 203.9 mg/dL to 97.6 mg/dL in Non-MetS group, p < 0.001), but %Change was not significantly different between the two groups (−44.1% vs. −51.6%, p = 0.099). Serum HDL-C and Apo A-I levels significantly increased in both groups, but no significant differences in %Change were found between the two groups (p = 0.591 in HDL-C; p = 0.432 in Apo A-I). HOMA-IR significantly decreased in MetS group (from 4.3 ± 4.0 to 3.1 ± 2.2, p = 0.011) but not in Non-MetS group (from 1.7 ± 1.0 to 1.5 ± 1.0, p = 0.553). %Change in liver enzyme levels was markedly decreased in MetS group than in Non-MetS group (alanine aminotransferase, −25.1% vs. −11.3%, p = 0.027; gamma-glutamyl transferase, −45.8% vs. −36.2%, p = 0.020). Although serum adiponectin levels did not change significantly in both groups, leptin levels significantly decreased in MetS group (from 18.5 ng/mL to 16.6 ng/mL, p = 0.004), but not in Non-MetS group (from 9.2 ng/mL to 9.0 ng/mL, p = 0.917). Conclusion Pemafibrate is as efficient in patients with MetS as in patients without MetS in improving the lipid and glucose metabolism. In addition, the use in MetS patients may be more effective in improving liver function and insulin resistance.