FDA Grants Accelerated Approval for Semaglutide in MASH Treatment, but Equity Gaps Persist in Clinical Trials
Key Insights
The FDA granted accelerated approval for semaglutide as a first-line treatment for moderate to severe MASH (search) in August 2025, based on phase 3 trial data showing 63% of patients achieved MASH resolution after 72 weeks.
Semaglutide works by addressing underlying MASH (search) causes including excess body fat and high blood sugar, leading to weight loss and improved metabolic health that allows liver healing.
Clinical trials for GLP-1 weight loss drugs show significant underrepresentation of Black and Hispanic patients, as well as patients with MASLD (search) and MASH (search) conditions.
The FDA granted accelerated approval for semaglutide as a first-line treatment for adults with moderate to severe metabolic dysfunction-associated steatohepatitis (MASH (search)) in August 2025, marking a significant milestone in liver disease treatment. The decision was based on positive data from an ongoing phase 3 clinical trial, with full approval expected once the trial is complete and additional data is reviewed.
Clinical Trial Results Drive Approval Decision
The FDA's accelerated approval came after early trial results demonstrated substantial efficacy. After 72 weeks, 63 percent of patients receiving semaglutide resolved their MASH (search) and didn't experience worse liver scarring or fibrosis, compared with 34 percent of those taking a placebo. Additionally, 37 percent of patients receiving semaglutide improved their liver fibrosis (search) without their MASH worsening, compared with 22 percent of those taking a placebo.
The ongoing trial is planned to last a total of 240 weeks, at which point the FDA will evaluate whether patients' improvements in liver inflammation and scarring observed after 72 weeks resulted in fewer deaths, liver transplants, and other liver-related health events.
Mechanism of Action in MASH Treatment
Semaglutide improves MASH (search) by addressing two of its underlying causes: excess body fat and high blood sugar. Both lead to excess fat accumulation and inflammation in the liver, which can lead to scarring or fibrosis over time.
"By inducing weight loss and improving metabolic health, semaglutide can decrease toxicity from fat accumulation and liver cell damage, allowing the liver to heal and achieve fibrosis regression," says Naim Alkhouri, MD, hematologist and chief medical officer at Summit Clinical Research in Phoenix.
Treatment Considerations for Different Patient Populations
Patients with Diabetes
The clinical trial exploring semaglutide as a MASH (search) treatment is testing a weekly 2.4 milligram dose, the maximum Wegovy dose, which is slightly higher than the maximum weekly 2 mg dose approved for Ozempic to treat diabetes (search). "Patients already on semaglutide for diabetes who want to treat MASH should talk to their provider to see if dose escalation is right for them," says A. Sidney Barritt IV, MD, director of hepatology at UNC School of Medicine in Chapel Hill, North Carolina.
Patients Without Obesity
Not everyone with MASH (search) has obesity (search), and semaglutide may not be as effective for these patients. "[Because] the semaglutide benefit is mostly indirect through control of weight and diabetes (search), patients without these comorbidities may not receive the same benefits," says Dr. Barritt. For these patients, alternative treatments like resmetirom may be worth considering.
Pediatric Patients
While semaglutide is approved to treat obesity (search) in children over 12 years old, it's not currently approved to treat MASH (search) in those under 18. MASH may be surprisingly common among children and teens, but treatment options remain limited to dietary changes and other lifestyle modifications.
Equity Gaps in Clinical Trial Representation
Despite the promising results, new research reveals significant representation gaps in GLP-1 weight loss trials. A systematic review of 149 clinical trials presented at The Liver Meeting found that Black and Hispanic individuals were substantially underrepresented compared to obesity (search) prevalence in these populations.
"As semaglutide and other GLP-1 receptor (search) agonists gain new indications, trial design and health system strategies must prioritize equity to ensure that the transformative benefits of these therapies reach populations who need them most," said Kimberly Ho, MD, internal medicine resident at The Warren Alpert Medical School of Brown University.
The analysis of 24 studies comprising 16,600 participants revealed that white participants were overrepresented, making up 69% of participants in all trials and 75% of U.S. trials. Although 50% of Black adults in the U.S. have obesity (search), Black participants made up just 6% of U.S. trials. Hispanic patients were also underrepresented, comprising 27% of participants in U.S. trials despite obesity prevalence of 45%.
Limited MASLD/MASH Representation in Trials
The research also found that patients with MASLD (search) and MASH (search) were underrepresented in trials. Although the prevalence of MASLD or MASH reaches about 40% in the U.S., only 18% of participants in trials had these conditions. The proportion was even lower in U.S.-based studies, where only 8% of participants had MASLD or MASH, compared with 26% of those in international studies.
Safety Considerations and Contraindications
Semaglutide carries specific contraindications and may not be appropriate for all patients. The medication should not be used by individuals with a personal or family history of medullary thyroid cancer, gastroparesis, multiple endocrine neoplasia type 2, or type 1 diabetes (search). Pregnant or breastfeeding women should also avoid the medication.
For patients with severe liver disease complications like cirrhosis (search), semaglutide's safety remains unclear. Some research suggests that rapid weight loss caused by semaglutide could potentially worsen liver scarring, though the mechanism is not yet understood.
Current Approval Scope
At present, semaglutide is only approved to treat MASH (search), not the milder form known as metabolic dysfunction-associated liver disease (MASLD (search)). However, since weight loss is a cornerstone of MASLD treatment, doctors may recommend semaglutide for overweight or obese patients with MASLD to reach a healthier weight and potentially improve liver health.
The medication is not considered effective for advanced liver complications and isn't currently recommended for patients with cirrhosis (search) or liver failure.