Treatment with pemafibrate ameliorates fatty liver index and atherogenic lipid profiles in Japanese patients with type 2 diabetes mellitus

Abstract

Background: Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, ameliorates hypertriglyceridemia. We investigated the effects of pemafibrate on steatotic liver disease (SLD) in relation to various atherogenic lipid profiles.

Methods: Thirty-nine Japanese patients with both type 2 diabetes mellitus (T2DM) and hypertriglyceridemia (men/women: 24/15, mean age: 58.2 years, median duration of diabetes: 5.0 years) were treated with 0.2 mg/day of pemafibrate for 12 months (M). SLD was estimated by fatty liver index (FLI), which is calculated by using waist circumference, body mass index and levels of triglycerides and γ-glutamyl transpeptidase.

Results: Treatment with pemafibrate significantly increased mean levels of high-density lipoprotein cholesterol (HDL-C) (baseline/3M/6M/12M: 46/55/55/54 mg/dL) and decreased median levels of triglycerides (baseline/3M/6M/12M: 211/112/99/98 mg/dL), non-HDL-C (146/128/125/121 mg/dL), small dense low-density lipoprotein cholesterol (45/33/30/30 mg/dL) and remnant-like particle cholesterol (8.1/2.6/2.3/2.4 mg/dL). There was no significant change in hemoglobin A1c level over time. FLI (mean ± standard deviation: 68.1 ± 21.9 vs. 39.6 ± 25.0, P < 0.001), but not FIB-4 index as a marker of hepatic fibrosis (median [interquartile range]: 1.04 [0.78-1.39] vs. 1.01 [0.68-1.36], P = 0.909), was significantly decreased by treatment with pemafibrate for 12M, and the proportion of patients with metabolic dysfunction-associated SLD (MASLD) was significantly decreased from 92.3% (baseline) to 61.5% (12M).

Conclusions: Pemafibrate ameliorates MASLD estimated by FLI in addition to various atherogenic lipid profiles in Japanese hypertriglyceridemia patients with T2DM in the past mean 5 years. An early intervention with pemafibrate might contribute to prevention of the development of MASLD and atherosclerotic cardiovascular disease.

Keywords: atherogenic lipid profiles; fatty liver index; metabolic dysfunction-associated steatotic liver disease; pemafibrate; type 2 diabetes.

Figure 1

Changes in lipid-related parameters after treatment with pemafibrate for 12 months. (A-I) Changes in lipid-related variables including triglycerides (TG) (A), non-high-density lipoprotein cholesterol (non-HDL-C) (B), low-density lipoprotein cholesterol (LDL-C) (C), high-density lipoprotein cholesterol (HDL-C) (D), very low-density lipoprotein cholesterol (VLDL-C) (E), intermediate-density lipoprotein cholesterol (IDL-C) (F), small dense low-density lipoprotein cholesterol (sdLDL-C) (G), remnant-like particle cholesterol (RLP-C) (H) and the ratio of apolipoprotein C3 to apolipoprotein C2 (ApoC3/ApoC2) (I) after treatment with 0.2 mg/day of pemafibrate for 12 months (M). Data are presented as medians with interquartile ranges. *p < 0.05 by the Friedman test with Dunn’s post-hoc test.

Figure 2

Change in FLI and prevalence of MASLD after treatment with pemafibrate for 12 months. (A-C) Comparisons of fatty liver index (FLI) before (at baseline) and 12 months (M) after the start of treatment with 0.2 mg/day of pemafibrate in all of the recruited patients (n = 39) (A) and in male patients (n = 24) (B) and female patients (n = 15) (C). Data are presented as box-and-whisker plots. *p < 0.001 by Wilcoxon’s signed-rank test. (D) Comparison of the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) before the start of treatment (at baseline) and that at 12 M after the start of treatment with pemafibrate. *p < 0.001 by McNamer’s test.