Semaglutide helps MASH
- A Phase 3 interim analysis found semaglutide resolved steatohepatitis and improved fibrosis versus placebo in patients with MASH. ( ) - The ESSENCE interim analysis reported benefits specifically in patients with MASH and stage 2–3 fibrosis. (hcplive.com) - Gastrointestinal disorders were the most common adverse events, while serious adverse event rates were similar between semaglutide and placebo. (hcplive.com)
Metabolic dysfunction-associated steatohepatitis, or MASH, is fatty liver disease with inflammation and scarring — and a Phase 3 trial found semaglutide improved both. (nejm.org) In the planned interim analysis of the ESSENCE trial, 800 of 1,197 enrolled patients had reached 72 weeks of follow-up. They had biopsy-defined MASH with stage 2 or 3 fibrosis, meaning moderate to advanced liver scarring short of cirrhosis. (abom.org) Patients were randomized 2-to-1 to once-weekly semaglutide 2.4 milligrams or placebo, after a 16-week dose-escalation period. The full study is ongoing for 240 weeks across 253 sites in 37 countries. (hcplive.com) At week 72, steatohepatitis resolved without worsening fibrosis in 62.9% of semaglutide patients versus 34.3% on placebo. Fibrosis improved without worsening steatohepatitis in 36.8% versus 22.4%, and both biopsy goals were met in 32.7% versus 16.1%. (abom.org) MASH has no symptoms for many patients until scarring is advanced, and untreated disease can progress to cirrhosis, liver cancer, or transplant. The trial targeted the group at highest near-term risk: adults with noncirrhotic disease and stage 2 or 3 fibrosis. (novonordisk.mediaroom.com) The results landed after the Food and Drug Administration approved resmetirom, sold as Rezdiffra, in March 2024 as the first drug for adults with noncirrhotic MASH and stage F2 to F3 fibrosis. That approval was accelerated and tied to biopsy improvement in MASH and fibrosis. (accessdata.fda.gov) Semaglutide is a glucagon-like peptide-1 receptor agonist already used for obesity and diabetes, and the liver results came with a mean body-weight change of minus 10.5% versus minus 2.0% on placebo. Researchers have also reported analyses suggesting some liver benefit tracks with weight loss and some does not. (abom.org; pmc.ncbi.nlm.nih.gov) The most common side effects in ESSENCE were gastrointestinal disorders, the same class of nausea and stomach symptoms already familiar from semaglutide’s diabetes and obesity use. Serious adverse-event rates were similar in the semaglutide and placebo groups. (hcplive.com) The FDA approved semaglutide 2.4 milligrams for noncirrhotic MASH with moderate-to-advanced fibrosis in August 2025, adding a second drug option for this disease. The ESSENCE readout that started as a 72-week interim analysis is now part of the evidence base doctors use to treat a liver disease that was long managed mostly with diet, exercise, and control of diabetes and cholesterol. (nejm.org)
