Semaglutide for Metabolic Dysfunction–Associated Steatohepatitis

This editorial highlights the interim results of the phase 3 ESSENCE trial, demonstrating semaglutide’s efficacy in treating MASH with stage 2 or 3 fibrosis. At 72 weeks, semaglutide (2.4 mg weekly) outperformed placebo in both primary endpoints: MASH resolution without worsening fibrosis (62.9% vs. 34.3%) and fibrosis improvement without worsening steatohepatitis (36.8% vs. 22.4%). The drug also improved cardiometabolic markers (e.g., weight loss, blood pressure, insulin resistance) with a safety profile consistent with prior GLP1 agonist trials. However, modest placebo-adjusted benefits and unresolved questions about long-term use, cost, and applicability to cirrhosis patients underscore the need for further research and combination therapies.

This editorial highlights the interim results of the phase 3 ESSENCE trial, demonstrating semaglutide’s efficacy in treating MASH with stage 2 or 3 fibrosis. At 72 weeks, semaglutide (2.4 mg weekly) outperformed placebo in both primary endpoints: MASH resolution without worsening fibrosis (62.9% vs. 34.3%) and fibrosis improvement without worsening steatohepatitis (36.8% vs. 22.4%). The drug also improved cardiometabolic markers (e.g., weight loss, blood pressure, insulin resistance) with a safety profile consistent with prior GLP1 agonist trials. However, modest placebo-adjusted benefits and unresolved questions about long-term use, cost, and applicability to cirrhosis patients underscore the need for further research and combination therapies.