Pharmacotherapy for Nonalcoholic Fatty Liver Disease: Comparative Efficacy

Abstract

Introduction: Nonalcoholic fatty liver disease (NAFLD) affects 25% of adults. No drug is FDA-approved, but vitamin E, pioglitazone, and GLP-1 agonists are commonly used off-label. Methods: Network meta-analysis of 19 RCTs (n=2,301) with biopsy-proven NAFLD without cirrhosis. Interventions: vitamin E (800 IU/day), pioglitazone (30-45 mg), semaglutide (0.4-1.0 mg/week). Primary outcome: ≥2-point improvement in NAS (steatosis, inflammation, ballooning) without fibrosis worsening. Results: Semaglutide showed highest efficacy (RR 2.34 vs placebo, 95% CI 1.68-3.26, NNT=6), followed by pioglitazone (RR 1.92, 95% CI 1.38-2.67) and vitamin E (RR 1.58, 95% CI 1.12-2.23). Weight loss was greatest with semaglutide (-9.2 kg). Adverse events: gastrointestinal with semaglutide (32% vs 12%). Discussion: GLP-1 agonists address both metabolic dysfunction and liver histology. Vitamin E remains an option for non-diabetic patients. Conclusion: Semaglutide is most effective for biopsy-proven NAFLD, though long-term safety and cost-effectiveness require further study.