Fenofibrate in Metabolic Dysfunction-associated Steatotic Liver Disease: A Systematic Review and Meta-analysis

Abstract Introduction: Fenofibrate forms the standard of care for managing hypertriglyceridemia. Many of these patients have associated metabolic dysfunction-associated steatotic liver disease (MASLD). No systematic review and meta-analysis (SRM) has analysed the impact of fenofibrate in MASLD. Hence, we undertook this SRM. Methods: Electronic databases were searched for randomised controlled trials (RCTs) involving MASLD patients receiving fenofibrate as an intervention and placebo/active comparator as control. The primary outcome was changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Secondary outcomes were alterations in liver fat (ultrasonography or magnetic resonance imaging), lipid parameters, and adverse events. Results: From initially screened 395 articles, data from 5 RCTs were analysed. Fenofibrate had comparable changes in ALT (mean difference [MD]-0.32 IU/L [95% confidence interval [CI]: −6.70–7.33]; P = 0.931; I 2 = 60%) and AST (MD-0.17 IU/L [95% CI: −3.83–3.48]; P = 0.932; I 2 = 31%) as compared to active controls (atorvastatin, omega-3 fatty acids [O3FA] and pioglitazone). Fenofibrate users had a greater increase in liver-fat content as compared to active controls (pioglitazone and O3FA) (MD 5.37 [95% CI: 0.30–10.44]; P = 0.041; I 2 = 85%). O3FA and pioglitazone use is associated with reduction in liver fat, which explains the apparent increase in liver fat with fenofibrate in our analysis. Fenofibrate was associated with a significantly greater decrease in triglycerides compared to active controls (MD-0.22 mmol/l [95% CI: −0.31–−0.12]; P < 0.001; I 2 = 0%). Fenofibrate was associated with comparable change in total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, weight, and waist circumference compared to active controls. Conclusion: This SRM provides us with reassuring safety data on use of fenofibrate in MASLD. Fenofibrate is largely MASLD neutral and continues to have good triglyceride lowering properties in MASLD.