Two New Drugs Are Changing the Treatment of Fatty Liver Disease

Until recently, treatment for metabolic dysfunction-associated steatohepatitis (MASH), the inflammatory form of fatty liver disease, depended primarily on weight loss, dietary changes, and exercise.

Although these approaches remain essential, we now have two FDA-approved medications that can improve liver inflammation and scarring (fibrosis). But these medications are not intended for everyone with fatty liver disease.

The first medication, Resmetirom, is approved for patients with MASH and moderate to advanced fibrosis (stages F2 and F3), but not cirrhosis. It works by activating thyroid hormone receptors in the liver, changing how the liver processes fat.

The second medication is semaglutide (Wegovy). Like resmetirom, semaglutide is approved for MASH with F2 or F3 fibrosis, but not cirrhosis. Interestingly, some of the liver benefits appear to occur independently of weight loss, possibly through reductions in metabolic inflammation.

Where do medications fit in the treatment of fatty liver disease? The first step after diagnosing MASLD is to determine how much liver scarring is present, usually beginning with a simple blood test calculation called FIB-4, followed by FibroScan or other testing when indicated.

For patients with little or no fibrosis (F0 or F1), treatment focuses on weight loss, a Mediterranean-style diet, regular exercise, and control of diabetes if present. Medications specifically approved for MASH are generally not indicated at this stage.

However, patients with MASH and moderate to advanced fibrosis (F2 or F3) should be evaluated for treatment with resmetirom or semaglutide in addition to lifestyle changes.

The choice depends partly on whether obesity and diabetes are major problems, which would favor semaglutide, or whether a liver-directed treatment without significant weight loss is preferred, favoring resmetirom. Importantly, patients with significant fibrosis should not have to wait for lifestyle changes to fail before medication is considered.

The take-home message is that MASH is becoming a treatable disease rather than one we simply monitor while encouraging weight loss.

For those with early fatty liver disease, lifestyle modification remains the foundation of treatment. For patients at the next stage of the disease, with significant fibrosis, medications can now supplement diet and exercise.

Diagnosing fatty liver is only the beginning. Determining whether significant fibrosis is present is the critical next step in deciding who needs medication in addition to lifestyle changes.

Source

Medscape Education, “Updates on Metabolic Dysfunction-Associated Steatohepatitis Treatment,” discussion between Jeffrey V. Lazarus, Dr.med, and Jörn M. Schattenberg, MD. Released June 18, 2026. Read the Medscape Education article

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