Focus on Semaglutide 2.4 mg/week for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis.

🥉 Top 5% JournalOct 27, 2025Liver international : official journal of the International Association for the Study of the Liver

Using Semaglutide to Treat Fatty Liver Disease

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Abstract

Subcutaneous semaglutide 2.4 mg/week shows significant improvements in hepatic steatosis and liver fibrosis in patients with metabolic dysfunction-associated steatohepatitis (MASH) and advanced fibrosis (stage F2/F3).

Treatment with semaglutide is associated with marked reductions in liver fat and disease activity.
Significant weight loss accompanies the hepatic benefits observed with semaglutide.
Improved metabolic outcomes, including better glucose control and lipid profiles, are noted alongside liver improvements.
Cardiovascular and renal health may also benefit from semaglutide treatment.
Gastrointestinal issues are the most common side effects, but no new safety concerns have been identified.
Long-term data on tolerability and clinical outcomes in MASH patients are still pending.

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Semaglutide has recently received conditional accelerated approval in the US for treatment of metabolic dysfunction-associated steatohepatitis (MASH) with significant or advanced liver fibrosis (stage F2/F3). Phase 2 and 3 clinical trials show that subcutaneous semaglutide 2.4 mg/week leads to significant improvements in hepatic steatosis, disease activity, resolution of MASH and reduction in liver fibrosis. These benefits parallel weight loss and are accompanied by improved metabolic outcomes, including better glucose control and lipid profiles, as well as consistent benefits for cardiovascular and renal health. The treatment's safety profile is manageable, with gastrointestinal issues being the most frequent side effects, and no new safety concerns have been identified. Data on long-term tolerability, treatment retention and clinical events are now awaited in people with MASH fibrosis. The evidence regarding semaglutide's ability to directly target the liver and improve liver damage in cirrhosis, and its impact on muscle mass in at-risk populations, remains limited. Thus, in patients with advanced disease, it should be viewed primarily as a therapy that modifies metabolic disease. Practically, semaglutide is most suitable as a first-line treatment to prevent liver complications for people with MASH and stage F2/F3 fibrosis with severe metabolic dysfunction, obesity, or type 2 diabetes who could benefit from both liver and cardiovascular-renal improvements. Treatment should be tailoured to each individual, with ongoing monitoring of body weight, serum aminotransferase levels and direct measurement of liver fat and stiffness to guide therapy.