Semaglutide improves liver fibrosis
- Novo Nordisk and investigators reported that once-weekly semaglutide 2.4 mg met both main 72-week goals in the Phase 3 ESSENCE trial for adults with biopsy-confirmed MASH and stage 2 or 3 liver fibrosis. - In the first 800 patients, 62.9% on semaglutide achieved MASH resolution without worse fibrosis versus 34.3% on placebo, while 36.8% versus 22.4% improved fibrosis without worse MASH. - The data fed an August 2025 Food and Drug Administration approval for Wegovy in MASH with fibrosis, extending semaglutide beyond obesity and diabetes. (ajmc.com)
Fat can build up in the liver for years without symptoms, then leave behind scar tissue that is much harder to reverse. In a Phase 3 trial, semaglutide improved both liver inflammation and scarring after 72 weeks. (nejm.org) (novonordisk.mediaroom.com) The disease is called metabolic dysfunction-associated steatohepatitis, or MASH. It is the more dangerous form of fatty liver disease, where excess fat is joined by liver-cell injury and inflammation that can progress to cirrhosis, liver cancer, or transplant. (nejm.org) (prnewswire.com) Semaglutide is a glucagon-like peptide-1 drug, or GLP-1, already used for obesity and diabetes. It lowers appetite, body weight, blood sugar, and several metabolic risks that often travel with MASH. (nejm.org) (kcl.ac.uk) The ESSENCE study randomly assigned 1,197 adults with biopsy-defined MASH and stage 2 or 3 fibrosis in a 2-to-1 ratio to weekly semaglutide 2.4 mg or placebo for 240 weeks. The published interim analysis covered the first 800 patients at week 72. (nejm.org) (pubmed.ncbi.nlm.nih.gov) The first main goal was clearing steatohepatitis without making fibrosis worse. That happened in 62.9% of semaglutide patients versus 34.3% on placebo, a difference of 28.7 percentage points. (novonordisk.mediaroom.com) (sciencedirect.com) The second main goal was improving fibrosis by at least one stage without making steatohepatitis worse. That happened in 36.8% of semaglutide patients versus 22.4% on placebo, a 14.4-point gap. (novonordisk.mediaroom.com) (emjreviews.com) More patients on semaglutide also hit both targets at once: 32.7% versus 16.1% on placebo. Average body weight fell 10.5% with semaglutide and 2.0% with placebo. (novonordisk.mediaroom.com) (appliedclinicaltrialsonline.com) Side effects looked familiar for a GLP-1 drug. Gastrointestinal problems were more common with semaglutide, while serious adverse events were reported in 13.4% of semaglutide patients and 19.1% of placebo patients. (appliedclinicaltrialsonline.com) (hcplive.com) The study mattered because liver scarring, not just fat in the liver, is tied to worse outcomes. Earlier semaglutide studies had shown strong effects on inflammation and weight, but not the same clear fibrosis win now seen in this larger trial. (nejm.org) (pubmed.ncbi.nlm.nih.gov) Regulators moved after the data. The Food and Drug Administration approved Wegovy in August 2025 for adults with MASH and moderate to advanced fibrosis, excluding cirrhosis, making it the first GLP-1 cleared for that use. (ajmc.com) The trial is still running to test harder outcomes over 240 weeks, including progression to cirrhosis and other liver complications. For now, the 72-week biopsy results show semaglutide did more than help patients lose weight. (nejm.org) (gi.org)
