Preferable effects of pemafibrate on liver function and fibrosis in subjects with type 2 diabetes complicated with liver damage

Background Pemafibrate has been reported to ameliorate lipid profiles and liver dysfunction. However, which patients derive benefit from the hepatoprotective effects of pemafibrate is unclear. Methods We conducted a sub-analysis of the PARM-T2D study where subjects with type 2 diabetes complicated by hypertriglyceridemia were prospectively treated with pemafibrate or conventional therapies for 52 weeks. From the original cohort, subjects who had metabolic-associated fatty liver disease without changing their treatment regimens for comorbidities were analyzed. Eligible subjects (n = 293) (average age 61.2 [+ or -] 11.7 years, 37.5% female) treated with pemafibrate (pemafibrate, n = 152) or controls who did not change their treatment regimens (controls, n = 141) were divided into three groups based on their alanine aminotransferase (ALT) levels: ALT [less than or equal to] upper normal limit (UNL) (pemafibrate, n = 65; controls, n = 50), UNL < ALT [less than or equal to] 2xUNL (pemafibrate, n = 58; controls, n = 54), and 2xUNL < ALT (pemafibrate, n = 29; controls, n = 27). Results Pemafibrate treatment significantly ameliorated ALT levels (from 29 to 22 U/L, p < 0.001 by Wilcoxon's signed-rank test) in the total cohort and subjects with high ALT levels (2xULN < ALT), and improved liver fibrosis as assessed by the Fibrosis-4 index (mean change - 0.05 (95% confidence interval: -0.22 to - 0.02), p < 0.05 versus baseline by the Mann-Whitney U-test and p < 0.05 versus the ALT [less than or equal to] UNL group by the Kruskal-Wallis test followed by Dunn's post-hoc analysis). Conclusions The hepatoprotective effects of pemafibrate were dominant in subjects with type 2 diabetes complicated with liver dysfunction. Trial registration This study was registered with the University Hospital Medical Information Network Center Clinical Trials Registry (UMIN000037385). Keywords: Pemafibrate, Liver function, Type 2 Diabetes