Effects of Pemafibrate on Serum Carnitine and Plasma Myostatin in Patients With Metabolic Dysfunction Associated Steatotic Liver Disease

Abstract

Background

Pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPARα) modulator (SPPARMα), has positive effects on liver-related markers (e.g., liver stiffness determined by magnetic resonance elastography and alanine aminotransferase) in the PEMA-FL study in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Patients with MASLD reportedly have a high rate of muscle mass loss; hence, the prevention and treatment of sarcopenia is important for patients with MASLD. PPARα may be involved in the expression of carnitine and myostatin, which are known muscle-related markers. We conducted a post-hoc analysis of the PEMA-FL study to investigate the effects of pemafibrate on carnitine and myostatin levels.

Methods

The PEMA-FL study, a double-blind, placebo-controlled, randomized, multicenter, Phase 2 trial, randomized 118 patients to either Pemafibrate 0.4 mg/day or placebo (1:1) group (orally, twice daily for 72 weeks). This post-hoc analysis examined the percentage change in total carnitine, free carnitine, acylcarnitine, and myostatin in the pemafibrate group compared to those in the placebo group. We examined the correlation between percentage changes in carnitine and myostatin levels.

Results

Pmafibrate significantly increased serum total carnitine and free carnitine levels from baseline compared to placebo at Week 48 (treatment difference 24.2%; p < 0.001, 27.3%; p < 0.001, respectively) with similar trends for serum acylcarnitine (treatment difference 10.7%). Pemafibrate significantly reduced plasma myostatin levels at Week 72 (treatment difference −11.0%; p < 0.01) from baseline. Analysis of the significant changes in free carnitine and myostatin levels by subgroups showed similar changes in almost all subgroups. The percent changes in the serum total carnitine, free carnitine and acylcarnitine, and plasma myostatin levels at 12 weeks demonstrated no obvious correlations (r = 0.337, r = 0.358, r = 0.077, respectively).

Conclusions

Pemafibrate increased the serum carnitine and decreased plasma myostatin levels in patients with MASLD, which may have potential application in the development and progression of sarcopenia, but there are no results on the effect on muscle mass. Further research is warranted to determine whether these changes in physiology can lead to clinical benefits in the prevention or treatment of sarcopenia in patients with MASLD.

Trial Registration: ClinicalTrials.gov identifier: NCT03350165.