Semaglutide for 72 Weeks: MASH Resolution in 62.9% vs 34.3% With Placebo

Interim results of a phase 3 trial reporting that semaglutide, a GLP-1 receptor agonist, improved liver tissue findings in patients with metabolic dysfunction-associated steatohepatitis (MASH) were published in NEJM. The ESSENCE trial was led by researchers at Virginia Commonwealth University in the United States.

1,197 patients confirmed by liver biopsy, 72-week interim analysis

The researchers are running a trial in which 1,197 patients with MASH and stage 2 to 3 fibrosis confirmed by liver biopsy are randomised 2 to 1 to receive once-weekly subcutaneous injections of semaglutide 2.4 mg or placebo for 240 weeks. This report covers the 72-week results for the first 800 patients enrolled, in a pre-planned interim analysis.

The proportion with resolution of steatohepatitis without worsening of fibrosis was 62.9% in the semaglutide group and 34.3% in the placebo group. The proportion with reduced fibrosis without worsening of steatohepatitis was 36.8% vs 22.4%, also a significant difference. The proportion with improvement in both measures together was 32.7% vs 16.1%, and body weight fell by an average of 10.5% and 2.0%. Gastrointestinal adverse events were more common in the semaglutide group.

Liver disease outcomes await the final analysis

The result shows in a large phase 3 trial that a weight-loss class of drugs can change liver tissue in steatohepatitis tied to metabolic disease. However, the 72-week tissue findings are surrogate markers, and clinical outcomes such as progression to cirrhosis or liver-related events must be confirmed in the 240-week final analysis. The steatohepatitis resolution rate in the placebo group, 34.3%, was also not low. The trial was funded by the developer.