Scientists Develop Promising New Drug to Combat Severe Fatty Liver Disease

A new experimental drug may have found a way to strike fatty liver disease at its source instead of simply treating the fallout.

Researchers at the University of California, San Diego School of Medicine reported that a drug called ION224 significantly improved liver health in people with metabolic dysfunction-associated steatohepatitis (MASH), a dangerous form of fatty liver disease closely linked to obesity and type 2 diabetes. The findings, published in The Lancet, are raising hopes for a more targeted treatment approach against a disease that can silently progress to cirrhosis, liver failure, or liver cancer.

MASH, previously known as NASH, develops when excess fat builds up inside liver cells, triggering inflammation and scarring over time. Current treatments mainly focus on weight loss and lifestyle changes, but ION224 works differently. The drug blocks an enzyme called DGAT2, which plays a key role in producing and storing fat inside the liver.

The Phase IIb clinical trial involved 160 adults in the United States with MASH and mild to moderate liver fibrosis. Participants received monthly injections of ION224 or a placebo over 51 weeks.

The results were encouraging. Around 60% of patients receiving the highest dose showed meaningful improvements in liver inflammation and fibrosis compared with placebo recipients. Researchers also reported that the treatment was generally well tolerated, with no major safety concerns linked to the drug.

Scientists say the findings are especially important because ION224 appeared to improve liver disease even without major weight loss. That means it could potentially work alongside popular GLP-1 weight-loss medications in future combination therapies.

Researchers caution that larger Phase III trials are still needed before the drug could become widely available. But experts say the study marks one of the strongest signs yet that directly targeting liver fat production may help slow or even reverse the progression of MASH.

REFERENCE: Rohit Loomba, Erin Morgan, Keyvan Yousefi, Dan Li, Richard Geary, Sanjay Bhanot, Naim Alkhouri. Antisense oligonucleotide DGAT-2 inhibitor, ION224, for metabolic dysfunction-associated steatohepatitis (ION224-CS2): results of a 51-week, multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet, 2025; 406 (10505): 821 DOI: 10.1016/S0140-6736(25)00979-1