Efficacy of GLP-1-based Therapies on Metabolic Dysfunction-associated Steatotic Liver Disease and Metabolic Dysfunction-associated Steatohepatitis: A Systematic Review and Meta-analysis.
Wang. Yahao Y; Zhou. Yue Y; Wang. Zhihong Z; Ni. Yunzhi Y; Prud'homme. Gerald J GJ; Wang. Qinghua Q
Key Findings
- GLP‑1RAs reduced liver fat content by an average of 5.2% after ~24 weeks of treatment.
- Retatrutide produced the strongest reduction in liver fat among the studied peptides.
- Treatment improved liver histology (steatosis, ballooning, inflammation) but did not significantly change fibrosis.
- Serum liver enzymes (ALT, AST, GGT) fell significantly, indicating less liver injury.
- Semaglutide showed the greatest improvement in liver stiffness, a non‑invasive fibrosis marker.
Practical Outcomes
- For biohackers aiming to improve metabolic and liver health, GLP‑1‑based peptides appear to be a useful tool for lowering liver fat and inflammation. Retatrutide looks especially promising, but it’s still early‑stage and may not be widely accessible. If you’re already using a GLP‑1RA (e.g., semaglutide or tirzepatide), you can expect added liver benefits alongside weight loss, but monitor liver enzymes and consult a clinician before adding or switching peptides.
Summary
A big review of 25 trials found that drugs that activate the GLP‑1 receptor – like liraglutide, semaglutide, tirzepatide and the newer peptide retatrutide – can cut liver fat by about 5% after roughly six months. Retatrutide showed the biggest drop in liver fat, and these drugs also improved liver inflammation and cell damage markers without hurting the liver.
Abstract
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. 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. 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. GLP-1RAs decreased liver fat deposition and improved histological steatosis, hepatocellular ballooning, and lobular inflammation, without worsening of fibrosis in MASLD and MASH.
Study Information
pubmed
2025
2025-09-16T00:00:00.000Z
10.1210/clinem/dgaf336
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