The First Approved Fatty Liver Medicine Improved Both Inflammation and Scarring

CATEGORY: GUT & DIGESTIVE HEALTH

Until 2024, a common liver disease had no approved medicine at all. The tablet that ended that run, resmetirom, earned its approval by clearing the disease’s hallmark inflammation in up to 29.9% of patients against 9.7% on placebo, and improving liver scarring in up to 25.9% against 14.2%, across 955 adults randomly assigned to drug or placebo for one year.¹ It is taken once a day. US regulators approved it in March 2024 for the form of the disease that has reached moderate to advanced scarring.

A Liver Disease That Rarely Announces Itself

The condition is now called MASH, short for metabolic dysfunction-associated steatohepatitis and formerly known as NASH. It starts when fat builds up inside liver cells. In some people that fat sets off persistent inflammation, and the liver patches the damage with scar tissue, called fibrosis. Scar on top of scar can end in cirrhosis, liver failure or liver cancer, usually after years with few symptoms or none. MASH keeps company with the metabolic conditions that are now widespread. Among the trial’s participants, 67% also had type 2 diabetes, and most had high blood pressure or abnormal cholesterol.

Two Biopsies, a Year Apart

Researchers at 245 centers in 15 countries enrolled 955 adults whose MASH and fibrosis had been confirmed by a liver biopsy, a test that takes a small sample of liver tissue for examination. A random allocation then sent each adult to resmetirom at 80 mg, resmetirom at 100 mg, or placebo, taken daily for 52 weeks. A second biopsy at the end let pathologists compare every liver against its own starting point. That comparison is how both headline outcomes were judged: whether the inflammatory disease resolved without the scarring worsening, and whether the scarring improved by at least one stage without the disease worsening.

Roughly One Patient in Four, Against One in Ten

Inflammation resolved in 25.9% of the 80 mg group and 29.9% of the 100 mg group, against 9.7% on placebo. Scarring improved by at least one stage in 24.2% and 25.9%, against 14.2%. Both at once, the strictest measure, happened in 14.2% and 16.0% versus 4.9%.¹ Resmetirom imitates thyroid hormone, but only at the receptor form concentrated in liver cells. Think of a letter addressed to a single door. It prods the liver into burning its excess fat without pushing up thyroid activity in the rest of the body. LDL cholesterol, the “bad” kind, fell 13.6% to 16.3% on the drug while barely moving on placebo.

What the Biopsies Cannot Say Yet

Diarrhea and nausea were the most common side effects, generally mild and short-lived. Diarrhea hit 27.0% to 33.4% of those on the drug against 15.6% on placebo. Of the higher-dose group, 6.8% quit over adverse effects, against 2.2% on placebo. The three groups had similar rates of serious adverse events.¹ Both headline outcomes were biopsy findings, not illness or survival. The same study runs on to 54 months to learn whether the drug prevents cirrhosis, liver failure and death, and the approval excludes people whose disease has already reached cirrhosis. A second medicine now points the same way. In 2025, a separate large randomized trial found that semaglutide, the diabetes and weight-loss drug, also resolved MASH and improved fibrosis more often than placebo.²

Key Takeaways

• Over a year, resmetirom resolved the liver inflammation of MASH in up to 29.9% of 955 trial participants, against 9.7% on placebo, and improved fibrosis in up to 25.9% against 14.2%.
• It became the first US-approved medicine for MASH with moderate to advanced fibrosis: a daily tablet that acts on thyroid-hormone receptors concentrated in the liver.
• What is proven so far rests on liver-tissue measures. Whether the drug prevents cirrhosis, liver failure or death is still being tested in the trial’s longer outcomes phase.
• A 2025 randomized trial of semaglutide showed the same pattern of benefit, which strengthens the case that this stage of fatty liver disease is treatable.

References

1. Harrison SA, Bedossa P, Guy CD, et al. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. New England Journal of Medicine. 2024;390(6):497–509. link
2. Sanyal AJ, et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction–Associated Steatohepatitis. New England Journal of Medicine. 2025;392(21):2089–2099. link