Semaglutide, the active ingredient in popular drugs Ozempic and Wegovy, is poised to add to its growing list of medical uses. In a large-scale clinical trial published today, semaglutide was found to be effective at treating a severe and relatively common form of liver disease.
Researchers in the U.S. and the U.K. led the Phase III trial, funded by the drug’s maker, Novo Nordisk. Compared to placebo, semaglutide substantially improved the outcomes of people with metabolic dysfunction associated steatohepatitis (MASH). The findings will pave the way for semaglutide and similar drugs to become frontline treatments for this chronic condition.
MASH is the most severe form of metabolic dysfunction-associated steatotic liver disease (MASLD). Both are characterized by an excess buildup of fat in the liver, which can lead to damaging inflammation and eventual permanent scarring, or cirrhosis. These conditions were formerly known as nonalcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD), respectively.
MASLD is the most common form of liver disease—affecting a quarter of adults in the U.S.—though it often doesn’t cause visible symptoms. Most people with MASLD don’t progress to MASH, but the condition still affects up to 6.5% of American adults. The cirrhosis caused by NASH can raise the risk of other severe complications, including hepatocellular carcinoma (the most common form of primary liver cancer) and outright liver failure.
MASLD/MASH can be caused by several factors, including a person’s genetics, but both obesity and diabetes are major contributors. About 75% of people who are overweight and 90% of people with severe obesity have MASLD; and between one-third to two-thirds of those with type 2 diabetes have it as well. Given this close relationship, scientists have hoped that semaglutide and similar drugs that mimic the hormone GLP-1 (already approved to treat obesity and diabetes) could be an effective treatment for MASLD/MASH as well.
Novo Nordisk’s Phase III trial, named ESSENCE, involved around 800 patients with MASH. The volunteers were randomly assigned to receive semaglutide (up to 2.4 milligrams, the highest dose currently approved for obesity treatment) or placebo over a 72-week period. Both groups also received lifestyle counseling.
By the study’s end, nearly two-thirds of people on semaglutide experienced a resolution of their steatohepatitis (liver inflammation accompanied by fat build-up)—about double the percentage of those who experienced the same while on placebo. People on the drug also experienced a greater improvement of liver fibrosis (a buildup of scar tissue) than those on placebo, and they lost more weight (about 10% on average). People experienced similar adverse effects on semaglutide as seen in past trials, which predominantly included gastrointestinal symptoms like nausea, diarrhea, and vomiting.
“I’ve been working with GLP-1 treatments for sixteen years and these results are hugely exciting. MASLD is a growing problem worldwide and this trial will provide real hope for patients with MASH,” said co-lead author Philip Newsome, director of the Roger Williams Institute of Liver Studies at King’s College London, in a statement from the university. “While these results must be treated with caution, the analysis shows semaglutide can be an effective tool to treat this advanced liver disease.”
The trial’s findings, published Wednesday in the New England Journal of Medicine, are almost certain to secure the drug’s approval for treating MASH from the Food and Drug Administration. The expected approval would represent the latest breakthrough for a condition that only recently had no available drug treatments. Just over a year ago, the FDA approved the first such drug, Rezdiffra from Madrigal Pharmaceuticals.
Rezdiffra is a bit different in terms of how it treats MASH. It targets a different receptor that more specifically prevents the build-up of fat in the liver without causing weight loss. But that’s likely a positive, since it should provide doctors and patients more treatment options to choose from, especially when people don’t respond well to one or the other.
Other GLP-1 drugs (including drugs that mimic other weight-related hormones) are being tested for MASH. So if things continue to go well, these drugs could soon revolutionize the treatment of MASH, just as they already have for obesity.