PLAINSBORO – November 08, 2026 -- Novo Nordisk reported that once-weekly semaglutide 2.4 mg improved liver enzymes and non-invasive markers of disease activity and fibrosis at week 72 in 106 adults with MASH, liver scarring and a BMI below 27 kg/m2, versus placebo.
The post hoc analysis of the phase 3 ESSENCE trial was presented orally at The Liver Meeting 2026 in Denver, Colorado.
Subgroup of 106 patients drawn from 800-patient interim analysis
The subgroup comes from the 800 randomized participants in the 72-week interim analysis of part 1 of ESSENCE. Measures that favored semaglutide included liver injury markers ALT and AST, along with FAST, ELF and PRO-C3. ELF and PRO-C3 are non-invasive fibrosis biomarkers and add fibrosis information alongside biopsy-based endpoints.
For VCTE-LSM, a liver stiffness measure, the 95% confidence interval included 1.0, so that result was not statistically distinct from placebo. Novo said the findings supplement the histologic data for this subgroup on both primary endpoints: resolution of steatohepatitis without worsening of fibrosis, and fibrosis improvement without worsening of steatohepatitis.
Novo flags exploratory nature of the data
The company described the analysis as hypothesis generating and said further work on the clinical validity of the results would be of value.
Michelle Skinner Moore, Vice President, Medical Affairs at Novo, said adults with a BMI below 27 have received less attention in MASH because the disease is often associated with obesity. Professor Jörn Schattenberg of Saarland University Medical Center said the data show a pattern across injury, activity and fibrosis measures and that "body size alone does not define MASH."
Underdiagnosis keeps MASH patient pool largely untreated
Novo cited more than 250 million people living with MASH. Nearly 90% remain undiagnosed, and the number of people in advanced stages is expected to rise more than 160% from 2015 to 2030. More than one in three people with overweight or obesity also have MASH, and more than 8 in 10 people with MASH live with obesity.
Confirmatory ESSENCE part 2 runs to 240 weeks
ESSENCE randomized 1,197 participants 2:1 to semaglutide 2.4 mg or placebo, on top of standard of care, for 240 weeks. Part 1 tested histologic improvement at 72 weeks in the first 800 patients. Part 2 is ongoing and will test whether semaglutide lowers the risk of liver-related clinical events at 240 weeks in adults with stage F2 or F3 fibrosis.
The FDA granted semaglutide 2.4 mg accelerated approval for adults with MASH and moderate-to-advanced fibrosis, excluding cirrhosis. Continued approval may depend on verifying clinical benefit in a confirmatory trial. The label carries a Boxed Warning for possible thyroid tumors, including cancer.