Plainsboro, New Jersey, USA, and Bagsværd, Denmark, November 8, 2026
Novo Nordisk has announced encouraging findings from a post-hoc analysis of its Phase 3 ESSENCE clinical trial, demonstrating improvements in several liver-related biomarkers among adults with metabolic dysfunction-associated steatohepatitis (MASH), liver scarring and a body mass index (BMI) below 27 kg/m². The analysis evaluated Wegovy (semaglutide 2.4 mg), administered as a once-weekly injection, compared with placebo over 72 weeks. The findings were presented during an oral scientific presentation at The Liver Meeting 2026, organized by the American Association for the Study of Liver Diseases (AASLD), in Denver, Colorado. The analysis focused on 106 adults with MASH and liver fibrosis who had a BMI below 27 kg/m², a population that has received comparatively less attention because MASH is frequently associated with overweight and obesity. Results showed favorable changes in multiple measures of liver injury, disease activity and fibrosis among participants receiving semaglutide compared with placebo. The findings provide additional information about the potential role of semaglutide in managing MASH across different body sizes. They also highlight the importance of recognizing liver disease in individuals who do not have an elevated BMI.
Semaglutide 2.4 mg Improves Multiple Liver Biomarkers
The post-hoc analysis examined liver-related measurements from participants enrolled in the ESSENCE Phase 3 trial. Of the 800 randomized participants included in the 72-week interim analysis of the first part of the study, 106 participants had a BMI below 27 kg/m². Researchers evaluated changes in liver enzymes, disease activity scores and non-invasive fibrosis biomarkers to understand the treatment’s effects on liver health. At week 72, participants receiving semaglutide 2.4 mg demonstrated favorable changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), two important enzymes used to assess liver injury. The estimated treatment ratio for ALT was 0.61, while the corresponding ratio for AST was 0.67, both favoring semaglutide over placebo. The analysis also showed improvements in the FibroScan-AST (FAST) score, with an estimated treatment difference of -0.13. These findings indicate favorable changes across multiple indicators of liver disease activity rather than improvements in a single laboratory measurement. The results provide additional evidence for evaluating semaglutide in people with MASH who have liver scarring despite having a BMI below the conventional overweight threshold.
Non-Invasive Fibrosis Markers Show Favorable Changes
In addition to liver enzyme improvements, the analysis evaluated non-invasive biomarkers associated with liver fibrosis. These included the Enhanced Liver Fibrosis (ELF) score, PRO-C3 and vibration-controlled transient elastography liver stiffness measurement (VCTE-LSM). The ELF score showed an estimated treatment difference of -0.45 in favor of semaglutide compared with placebo. PRO-C3, a biomarker associated with type III collagen formation and liver fibrosis activity, demonstrated an estimated treatment ratio of 0.82. These findings suggest favorable changes in biomarkers associated with liver scarring and extracellular matrix remodeling. The VCTE-LSM measurement also numerically favored semaglutide, with an estimated treatment ratio of 0.88. However, its 95% confidence interval included 1.0, meaning that this particular result did not establish a statistically significant difference between treatment groups. Together, the biomarker findings supplement previously reported histological results from the ESSENCE trial subgroup. The primary histological endpoints included resolution of steatohepatitis without worsening liver fibrosis and improvement in liver fibrosis without worsening steatohepatitis. Researchers emphasized that examining several different measures can provide a broader understanding of treatment-associated changes in liver health.
Advertisement
Novo Nordisk Continues MASH Clinical Development
The latest findings strengthen Novo Nordisk’s ongoing research program investigating semaglutide for MASH and other metabolic diseases. The ESSENCE Phase 3 trial is evaluating once-weekly subcutaneous semaglutide 2.4 mg in adults with MASH and moderate-to-advanced liver fibrosis, corresponding to fibrosis stages F2 and F3. The overall study enrolled 1,197 participants randomized in a 2:1 ratio to receive semaglutide or placebo alongside standard care. The trial consists of two parts, with the first evaluating liver histological improvements at 72 weeks and the second continuing to assess longer-term liver-related clinical outcomes over 240 weeks. Novo Nordisk highlighted that the latest post-hoc analysis is exploratory and hypothesis-generating. Therefore, additional research is needed to establish the clinical significance of the observed biomarker changes in this specific population. The findings reinforce the importance of recognizing MASH regardless of body weight and expanding clinical research into liver disease across diverse patient populations. Overall, the ESSENCE analysis represents another important development in Novo Nordisk’s clinical research efforts, providing further insights into semaglutide 2.4 mg and its potential role in addressing MASH with liver scarring.
Source: Novo Nordisk press release
