The FDA approved semaglutide (Wegovy, Novo Nordisk) in conjunction with diet and exercise for the treatment of metabolic dysfunction–associated steatohepatitis with moderate to advanced fibrosis after clinical trial data showed the drug improved resolution of MASH and liver fibrosis better than placebo.
The approval makes the glucagon-like peptide-1 receptor agonist the second drug approved for MASH, which is estimated to affect more than 40% of adults by 2050 (JAMA Netw Open 2025;8[1]:e2454707). Resmetirom (Rezdiffra, Madrigal), a partial agonist of thyroid hormone receptor beta, was approved for MASH in 2024, and several other potential therapies are being investigated in clinical trials.
The ESSENCE study (ClinicalTrials.gov Identifier: 04822181) evaluated once-weekly semaglutide in patients with MASH and fibrosis that had advanced to stage F2 or F3. The investigators found that 63% had a resolution of MASH without worsening of fibrosis, compared with 34% of those who received placebo. A secondary end point was improvement of fibrosis with no worsening of steatohepatitis, seen in 37% of the patients who took semaglutide and 22% of those taking placebo.
The drug’s mechanism of action in MASH is not fully understood but may involve pathways mediated by weight loss, according to the prescribing information. The drug is administered once weekly via subcutaneous injection, and dosing is the same for patients with MASH as it is for overweight/obesity: 0.25 mg titrated up by 0.25 mg every four weeks to the maintenance dose of 2.4 mg weekly, which can be decreased to 1.7 mg weekly for those who cannot tolerate the full dose.
Adverse effects are similar to those seen in patients taking semaglutide for other indications: nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, dyspepsia, dizziness, abdominal distension, eructation, hypoglycemia in patients with type 2 diabetes, flatulence, gastroenteritis, gastroesophageal reflux disease and nasopharyngitis. The drug is contraindicated in patients with a personal or family history of medullary thyroid cancer or type 2 multiple endocrine neoplasia.
—GEN Staff