For years, a doctor who diagnosed a patient with MASH had little to offer beyond advice. Lose weight. Maybe consider bariatric surgery. Vitamin E or pioglitazone, a diabetes medicine, were tried at times, though Dr. Jason Pan, a transplant hepatologist at UCLA Health’s Pfleger Liver Institute, says doctors did not believe those therapies were effective.
That has changed. The FDA has now approved two medicines for adults whose MASH, short for metabolic dysfunction-associated steatohepatitis, has reached moderate to advanced fibrosis: resmetirom and semaglutide. “The hepatology community has been managing MASLD and MASH for many years without any FDA-approved medications,” Pan said.
What the disease does
MASH is the more severe form of fatty liver disease. Fat builds up, the liver becomes inflamed and damaged, and over time scarring sets in. Severe scarring can lead to cirrhosis and liver failure, and the disease now ranks among the main drivers of cirrhosis and of liver transplants. Liver cancer is a risk too, and so are cardiac problems: heart disease, heart attack, stroke.
The wider condition, MASLD, is common. It touches one in three people across the globe, roughly 100 million of them American adults. Many have no symptoms. In about 20% of them it advances to MASH. A doctor should get suspicious when a patient has obesity, high cholesterol, insulin resistance or type 2 diabetes.
Two drugs, two paths
Resmetirom, sold as Rezdiffra by Madrigal Pharmaceuticals, is a once-daily pill that targets the thyroid hormone receptor-β. Semaglutide, the GLP-1 drug Novo Nordisk sells as Wegovy, received accelerated approval for this use, as reported by the American Journal of Managed Care on August 18, 2025. The 2.4 mg injection does not cover patients who already have cirrhosis, and the label calls for eating fewer calories and moving more. UCLA Health notes semaglutide also comes as a daily pill.
The approval rested on the first part of the phase 3 ESSENCE trial, which enrolled adults with stage F2 to F3 fibrosis. By week 72, about 63% of those given semaglutide saw their steatohepatitis resolve without worse fibrosis, against 34% on placebo. Fibrosis improved without worse steatohepatitis in 37% of the semaglutide group, versus 22% on placebo. Results from the trial’s second part are expected in 2029.
Choosing between them
Here is the practical problem. Neither drug has been tested head to head with the other. So a UCLA Health team led by Pan and senior author Dr. Sammy Saab wrote a review, published in Digestive Diseases and Sciences, with an algorithm that weighs a patient’s other conditions, risk factors and preferences.
“We’re excited to have not one but two drugs that are available to our patients,” said Saab, who runs the adult liver transplant program at UCLA Health. “Both are effective. But there may be nuances that favor one over the other in a particular patient.” At UCLA, hepatologists work alongside cardiologists and nutrition experts. “We need to make sure we look at the big picture,” he said.
Started in time, either drug can slow the damage, even reverse it, before cirrhosis arrives.
Sources
- Two FDA-approved drugs for MASH: How should doctors choose? (UCLA Health)
- FDA Approves Semaglutide for MASH With Fibrosis (AJMC)
