Efficacy of GLP-1-based Therapies on Metabolic Dysfunction-associated Steatotic Liver Disease and Metabolic Dysfunction-associated Steatohepatitis: A Systematic Review and Meta-analysis

Jun 9, 2025The Journal of clinical endocrinology and metabolism

Effectiveness of GLP-1 Treatments for Fatty Liver Disease Linked to Metabolic Problems and Its Inflammatory Form

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Abstract

GLP-1 receptor agonists led to a 5.21% reduction in liver fat content after a median treatment duration of 24 weeks.

Treatment with GLP-1 receptor agonists resulted in significant histological improvements in steatosis, hepatocellular ballooning, and lobular inflammation.
Fibrosis improvement was nonsignificant, with tirzepatide showing more robust evidence than semaglutide and liraglutide.
Serum liver enzymes such as alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transferase were significantly decreased compared to control.
Liver stiffness was significantly improved, with the most notable effects observed with semaglutide.
No drug-related liver adverse effects were reported during the study.

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OBJECTIVE: New therapies are urgently needed for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). We conducted this systematic review and meta-analysis to evaluate the therapeutic effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on MASLD/MASH.

METHODS: We searched PubMed, Embase, and Cochrane Library databases to identify randomized controlled trials (RCTs) that compared GLP-1RAs with placebo or active agents with respect to the efficacy in patients with MASLD/MASH. The effects of GLP-1RAs on liver fat content (LFC) by imaging, liver histology, serum liver enzymes, and noninvasive fibrosis indexes [Fibrosis-4, nonalcoholic fatty liver disease fibrosis score, cytokeratin 18, procollagen III, and liver stiffness) were evaluated. Mean differences and risk ratios with 95% confidence intervals were pooled using a random-effect model.

RESULTS: Twenty-five RCTs involving 2600 patients who used GLP-1RAs including liraglutide, exenatide, dulaglutide, semaglutide, tirzepatide, efinopegdutide, survodutide, and retatrutide were included. Overall, GLP-1RAs treatment for a median of 24 weeks demonstrated a significant reduction in LFC by 5.21%, with retatrutide displaying the most obvious treatment effects. GLP-1RAs treatment induced significant histological improvements in steatosis, hepatocellular ballooning, and lobular inflammation but nonsignificantly improved fibrosis, with the evidence for tirzepatide more robust than that for semaglutide and liraglutide. GLP-1RAs treatment significantly decreased serum alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transferase compared with control. GLP-1RAs also significantly improved liver stiffness, with semaglutide displaying the most obvious treatment effect. No drug-related adverse effects involving the liver were observed.

CONCLUSION: GLP-1RAs decreased liver fat deposition and improved histological steatosis, hepatocellular ballooning, and lobular inflammation, without worsening of fibrosis in MASLD and MASH.

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Efficacy of GLP-1-based Therapies on Metabolic Dysfunction-associated Steatotic Liver Disease and Metabolic Dysfunction-associated Steatohepatitis: A Systematic Review and Meta-analysis

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