A groundbreaking international study has revealed that semaglutide, the active compound in popular weight-loss medications Wegovy and Ozempic, shows remarkable effectiveness in treating metabolic dysfunction-associated steatohepatitis (MASH), a severe liver disease affecting approximately 15 million adults in the United States alone.
The Phase 3 clinical trial results, published Wednesday in the New England Journal of Medicine, demonstrate that semaglutide can not only halt the progression of MASH but potentially reverse liver damage in many patients.
Significant Improvements in Liver Health
The study, known as the ESSENCE trial (Effect of Semaglutide in Subjects with Non-cirrhotic Non-alcoholic Steatohepatitis), included 800 adults with moderate to advanced liver scarring from MASH. Participants received either weekly 2.4 mg injections of semaglutide or a placebo over 72 weeks.
The results were striking:
- Nearly 63% of patients receiving semaglutide experienced a reduction in liver inflammation without worsening scarring, compared to only 34% in the placebo group
- Almost 37% of semaglutide users showed reduced liver scarring, versus approximately 22% in the placebo group
- About one-third of patients on semaglutide achieved both inflammation reduction and scarring improvement—more than double the rate seen in the placebo group
"The results from this landmark study across 37 countries provide strong evidence that semaglutide can help patients with MASH by not only improving liver health, but also addressing the underlying metabolic issues that contribute to the disease," said Dr. Arun Sanyal, lead author and director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University.
Understanding MASH and Its Impact
MASH develops when excessive fat accumulates in the liver, leading to inflammation, cell damage, and scarring. The condition is closely linked with obesity and Type 2 diabetes, both of which are increasing in prevalence.
Dr. Vandana Khungar, a hepatologist at Yale New Haven Hospital who was not involved with the study, explained that inflammation and fat buildup in the liver are major factors causing scarring in MASH patients, which can ultimately lead to liver failure, necessitate transplantation, or result in death.
MASH has become one of the most common reasons for liver transplants nationwide, underscoring the urgent need for effective treatments. Currently, there is only one FDA-approved treatment for the condition.
Beyond Liver Benefits
The study also found that semaglutide provided additional health benefits beyond liver improvement. Participants experienced:
- Significant weight loss
- Improved liver function markers
- Enhanced overall cardiovascular health
These findings are particularly relevant given the strong connection between MASH and other metabolic conditions, including obesity, type 2 diabetes, and hypertension.
Safety Profile and Tolerability
Most participants tolerated semaglutide well, with nearly 90% remaining on the medication throughout the 72-week trial period. The most common side effects were mild digestive issues, primarily nausea, with no significant differences in serious adverse events between the treatment and placebo groups.
Looking Toward Regulatory Approval
Semaglutide is not currently approved to treat MASH in the United States. However, Novo Nordisk, the pharmaceutical company that manufactures Ozempic and Wegovy, has indicated plans to seek regulatory approval for this indication later this year.
"If approved, this could offer an additional therapeutic option for patients with MASH and fibrosis," Dr. Sanyal noted. "This is crucial, given the strong link between MASH and cardiovascular, metabolic, and renal conditions, where semaglutide has already shown established health benefits."
Ongoing Research
The ESSENCE trial continues with a second phase, in which researchers led by Dr. Sanyal will follow nearly 1,200 participants from 37 countries for up to five years. This extended study aims to gather comprehensive data on semaglutide's impact on long-term liver complications.
"The ESSENCE data may represent key findings for patients in the treatment of MASH, which is estimated to affect about one in 20 adults in the U.S.," said Dr. Sanyal. "By treating both liver disease and its metabolic causes, semaglutide offers a promising new approach for millions of patients."
As obesity and related metabolic disorders continue to rise globally, these findings represent a potentially significant advancement in addressing one of their most serious complications, offering hope to millions affected by this progressive liver disease.
