Effects of a novel selective peroxisome proliferator-activated receptor-α modulator, pemafibrate, on hepatic and peripheral glucose uptake in patients with hypertriglyceridemia and insulin resistance

Abstract

Aims/Introduction: Pemafibrate is a novel selective peroxisome proliferator-activated receptor-α modulator with potent triglyceride-lowering and high-density lipoprotein cholesterol-raising effects. We showed that pemafibrate decreased the homeostatic model assessment for insulin resistance in patients with dyslipidemia. To investigate how pemafibrate improves insulin sensitivity, we used a hyperinsulinemic-euglycemic clamp technique to determine the splanchnic and peripheral glucose uptake in patients with hypertriglyceridemia and insulin resistance. Materials and Methods: A total of 27 patients with hypertriglyceridemia and insulin resistance were randomly assigned to receive pemafibrate (0.4 mg/day, b.i.d.) or placebo treatment for 12 weeks. The hyperinsulinemic-euglycemic clamp test combined with oral glucose loading was carried out at weeks 0 and 12 to evaluate the splanchnic and peripheral glucose uptake. Results: Pemafibrate, but not the placebo, significantly increased the splanchnic glucose uptake rate from baseline (19.6 ± 5.9% with P = 0.005 and 2.1 ± 7.4% with P = 0.78, respectively), although no significant difference between the groups was observed (P = 0.084). Conversely, peripheral glucose uptake rate was not significantly altered. Pemafibrate, compared with the placebo, significantly decreased plasma triglycerides (−61.4 ± 16.4% vs −2.5 ± 41.4%, P = 0.001), free fatty acids (−24.8 ± 23.2% vs 2.0 ± 26.8%, P = 0.016) and gamma-glutamyl transpeptidase (−30 ± 46 vs 10 ± 19 U/L, P = 0.009) levels, and significantly increased fibroblast growth factor 21 (457.7 ± 402.1 vs −41.7 ± 37.4 pg/mL, P = 0.007) levels. Conclusions: Pemafibrate increased splanchnic glucose uptake from baseline in patients with hypertriglyceridemia.