Therapeutic Effects of Glucagon-like Peptide-1 Receptor Agonists in Non-Alcoholic Fatty Liver Disease: A Systematic Review

In a systematic review of 12 studies, GLP-1 receptor agonists such as semaglutide and liraglutide consistently reduced hepatic fat in adults with NAFLD/MASLD, with the strongest histological benefit being steatohepatitis resolution in non-cirrhotic MASH. Fibrosis improvements were mixed and limited in established cirrhosis, and long-term outcomes remain uncertain.

Systematic review. Population: Adults with NAFLD, NASH, MASLD, or MASH. Interventions: semaglutide; liraglutide; dulaglutide; beinaglutide.

Twelve studies were included. Hepatic fat was reduced with semaglutide, liraglutide, dulaglutide, and beinaglutide. Liver enzyme improvements were less consistent. Steatohepatitis resolution in non-cirrhotic MASH was the strongest histological benefit. Fibrosis findings were mixed, with the greatest benefit in F2-F3 MASH and limited improvement in established cirrhosis. Gastrointestinal symptoms were the most common adverse effects.

For researchers studying semaglutide or liraglutide, this paper summarizes the evidence on their effects on liver fat and histology in NAFLD/MASH. It does not establish comparative efficacy between the drugs, dosing, or long-term outcomes, and the mixed fibrosis data mean effects on advanced disease remain unclear.

Key findings

• The review included 12 studies.
• Hepatic fat reduction was the most consistent outcome, seen with semaglutide, liraglutide, dulaglutide, and beinaglutide.
• Liver enzyme improvements, especially alanine aminotransferase, were less consistent than fat reduction.
• Histological benefits were strongest for steatohepatitis resolution in non-cirrhotic MASH.
• Fibrosis improvements were greatest in F2-F3 MASH, with limited improvement in established cirrhosis.
• Gastrointestinal symptoms were the most common adverse effects.

Limitations

• Narrative synthesis was used because of heterogeneity in populations, designs, and outcomes, limiting quantitative conclusions.
• Effects on advanced fibrosis and long-term outcomes remain uncertain, as the authors note.
• Conclusions depend on the quality and reporting of the 12 included studies, which is not described in the abstract.

The record

• Journal: International journal of molecular sciences 27(12): 5618
• Published: 2026-06-22
• PMID: 42353331 — DOI: 10.3390/ijms27125618
• MeSH terms: Liver, Animals, Humans, Recombinant Fusion Proteins, Immunoglobulin Fc Fragments, Glucagon-Like Peptides, Non-alcoholic Fatty Liver Disease, Glucagon-Like Peptide-1 Receptor, Liraglutide, Glucagon-Like Peptide-1 Receptor Agonists, Semaglutide
• Author countries: Bahrain

Peptide profiles: Semaglutide, Liraglutide.

All indexed evidence: Semaglutide trials & papers, Liraglutide trials & papers.

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