World journal of gastroenterologySep 30, 2025

How well and how safely weight-loss drugs work in fatty liver disease linked to metabolic problems

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 1, 2026

Abstract

The increasing prevalence of obesity is closely linked to rising cases of metabolic dysfunction-associated steatotic liver disease (MASLD) and its severe form, metabolic dysfunction-associated steatohepatitis (MASH).

Anti-obesity medications (AOMs) may have complex interactions with altered liver metabolism in individuals with MASLD/MASH.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as liraglutide and semaglutide, are associated with reductions in liver fat and improvements in liver enzyme levels.
Tirzepatide, a dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonist, may provide superior weight loss effects but has limited data on liver health outcomes.
Retatrutide, a triple agonist, has shown the most significant metabolic effects so far, though its effects on liver tissue are not well studied.
Caution is advised when using other AOMs like bupropion-naltrexone and phentermine-topiramate due to potential liver toxicity.
Advanced MASLD may change how drugs are processed in the body, necessitating personalized treatment approaches.

Simplified

Obesity is a major driver of metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH). As the global prevalence of obesity continues to rise, the burden of MASLD/MASH is increasing, posing significant challenges to healthcare systems. The use of anti-obesity medications (AOMs) in this population is complex due to altered hepatic metabolism, safety concerns, and potential hepatotoxicity. Recent advances in pharmacologic agents, such as glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs), dual GLP-1/glucose-gastric inhibitory polypeptide (GIP) agonists, and triple GLP-1/GIP/glucagon agonists, have shown promising metabolic effects in the general population. Among these, GLP-1 RAs (, liraglutide and semaglutide) consistently demonstrate hepatic benefits, including reductions in hepatic steatosis, improvements in liver enzyme profiles, and attenuation of fibrosis progression. Tirzepatide, a dual GLP-1/GIP agonist, has shown superior weight loss effects compared to GLP-1 receptor agonist monotherapy, with emerging but still limited data on hepatic outcomes in MASLD/MASH. Retatrutide, a triple agonist, has produced the most pronounced metabolic effects to date, although its impact on liver histology remains underexplored. Other AOMs, such as bupropion-naltrexone and phentermine-topiramate, require cautious use due to potential hepatotoxicity. Importantly, advanced MASLD may alter drug pharmacokinetics, underscoring the need for individualized therapy and close monitoring. This review provides an updated synthesis of the efficacy and safety of current and emerging AOMs in patients with MASLD/MASH and highlights the urgent need for further research to define optimal pharmacological strategies in this high-risk population. e.g.

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Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

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How well and how safely weight-loss drugs work in fatty liver disease linked to metabolic problems

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