Journal of diabetes investigation 2018 03 30() doi 10.1111/jdi.12845
Pemafibrate (K-877) is a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα) with potent triglyceride (TG)-lowering and high-density lipoprotein cholesterol-raising effects. We showed that pemafibrate decreased the homeostasis model assessment for insulin resistance (HOMA-IR) 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, twice daily) or placebo treatment for 12 weeks. The hyperinsulinemic-euglycemic clamp test combined with oral glucose loading was performed at weeks 0 and 12 to evaluate the splanchnic and peripheral glucose uptake.
Pemafibrate, but not 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 placebo, significantly decreased plasma TGs (-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 (FGF21) (457.7±402.1 vs. -41.7±37.4 pg/ml, p=0.007) levels.
Pemafibrate increased splanchnic glucose uptake from baseline in patients with hypertriglyceridemia. This article is protected by copyright. All rights reserved.