Novo post hoc analysis finds Wegovy® 2.4 mg was associated with improvements in liver markers in adults with MASH with liver scarring and a BMI less than 27 kg/m2, presented at The Liver Meeting® (AASLD) 2026

• A post hoc analysis of adults with MASH and liver scarring with a BMI below 27 kg/m² found that measures of liver injury, fibrosis, and disease activity improved at week 72 among participants receiving semaglutide 2.4 mg once weekly injection versus placebo
• Non-invasive fibrosis biomarkers, including ELF and PRO-C3, also favored semaglutide 2.4 mg versus placebo, providing information on fibrosis in addition to biopsy-based endpoints
• Together with the ESSENCE histologic results, these findings add to the data on semaglutide 2.4 mg in people with MASH with liver scarring and a BMI below 27 kg/m², a population that may be overlooked because MASH is often associated with obesity

PLAINSBORO, N.J. and BAGSVÆRD, Denmark, Nov. 8, 2026 /PRNewswire/ -- Today, Novo Nordisk announced results from a post hoc analysis of the phase 3 ESSENCE trial. The analysis included a subgroup of 106 adults with metabolic dysfunction-associated steatohepatitis (MASH) and liver scarring who had a BMI below 27 kg/m². At week 72, multiple liver-related measures improved among participants receiving once-weekly semaglutide 2.4 mg injection compared with placebo, including liver enzymes and non-invasive markers of disease activity and fibrosis. Results were presented in an oral presentation at The Liver Meeting^® 2026 in Denver, Colorado.¹

"MASH can affect people of any body type. Its symptoms are often silent and, when the disease goes undiagnosed and untreated, it can lead to serious health complications," said Michelle Skinner Moore, PhD, MBA, Vice President, Medical Affairs at Novo. "This analysis shines a light on adults with a BMI below 27, a group that has received less attention in the MASH conversation because the disease is often associated with obesity. By examining markers of liver injury, disease activity, and fibrosis, in people taking semaglutide 2.4 mg, we gained more insights into this population, which may help inform care for people living with MASH."

Of the 800 randomized participants included in the 72-week interim analysis of part 1 of the ESSENCE trial, 106 had a BMI below 27 kg/m². Estimated treatment effects at week 72 are shown below.

Week 72 liver-related parameters in adults with MASH with liver scarring and a BMI < 27 kg/m²

*Values are estimated semaglutide 2.4 mg versus placebo effects with 95% confidence intervals. ETR = estimated treatment ratio; ETD = estimated treatment difference. ETR values below 1 and ETD values below 0 favor semaglutide 2.4 mg.
^†The 95% CI for VCTE-LSM included 1.0.

ALT = alanine aminotransferase; AST = aspartate aminotransferase; FAST = FibroScan-AST; ELF = Enhanced Liver Fibrosis; PRO-C3 = marker of type III collagen formation; VCTE-LSM = vibration-controlled transient elastography liver stiffness measurement.¹

Exploratory post hoc analyses are hypothesis generating, and further work investigating the clinical validity of these results would be of value.

The findings supplement the histologic data reported in this subgroup for both primary endpoints, resolution of steatohepatitis without worsening of liver fibrosis and improvement in liver fibrosis without worsening of steatohepatitis.¹

"This analysis is not about any single biomarker, but suggests a pattern across measures of liver injury, disease activity and fibrosis," said Professor Jörn Schattenberg, Director of the Department of Medicine II, Gastroenterology & Hepatology at the Saarland University Medical Center in Homburg and the University of the Saarland in Germany. "Together with the histologic findings, these data reinforce a crucial message: body size alone does not define MASH, and it should not define for whom MASH is taken seriously."

About the ESSENCE trial
ESSENCE is an ongoing phase 3 trial evaluating the effect of once-weekly subcutaneous semaglutide 2.4 mg injection in adults with MASH with moderate-to-advanced liver fibrosis (stage F2 or F3^†). It is a two-part trial in which 1,197 participants were randomized 2:1 to receive semaglutide 2.4 mg or placebo, on top of standard of care, for 240 weeks.² 

In part 1, the objective was to demonstrate that treatment with semaglutide 2.4 mg improves liver histology at 72 weeks compared with placebo, based on biopsy sampling from the first 800 randomized patients. In part 2, which is ongoing, the primary objective is to demonstrate that treatment with semaglutide 2.4 mg lowers the risk of liver-related clinical events compared to placebo in adults with MASH and moderate-to-advanced liver fibrosis at 240 weeks.³

About metabolic dysfunction-associated steatohepatitis (MASH)
MASH is a serious, progressive, metabolic disease affecting the liver, which can be fatal if not managed properly.⁴ More than 250 million people live with MASH,⁵ and the number of individuals in advanced stages of the disease is expected to increase over 160% from 2015 to 2030.⁶ Of those living with overweight or obesity, more than one in three also have MASH.⁷ And of those currently living with MASH, more than 40% have type 2 diabetes, and more than 8 in 10 also live with obesity.⁸ People living with MASH often have many other health-related comorbidities,⁹ such as cardiovascular disease, which is the leading cause of death in people with MASH.^10,11

MASH is largely a silent disease due to few and unspecific symptoms in its early stages,⁴ where nearly 90% of people with MASH remain undiagnosed.¹² Once MASH progresses to late stages, there is increased mortality and morbidity, including potential for cirrhosis, liver cancer, and need for liver transplant.¹³

About semaglutide 2.4 mg once weekly injection in metabolic dysfunction-associated steatohepatitis (MASH)
Semaglutide 2.4 mg is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) FDA-approved under accelerated approval to treat adults with MASH with moderate-to-advanced liver scarring (fibrosis), but not with cirrhosis of the liver, in conjunction with a reduced calorie diet and increased physical activity.¹³ This accelerated approval is based on improvement of MASH and liver scarring (fibrosis).¹³ Continued approval for this indication may be contingent upon the verification and description of clinical benefit in a confirmatory trial.¹⁴ Novo is investigating semaglutide 2.4 mg in the ongoing ESSENCE phase 3 trial, evaluating the effect of once-weekly subcutaneous semaglutide 2.4 mg in adults with MASH with moderate-to-advanced liver scarring (fibrosis) (consistent with stage F2 or F3^†).¹⁴

It is important to note that semaglutide 2.4 mg injection has a Boxed Warning for possible thyroid tumors, including cancer, and should not be used in those with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2). The most common side effects of semaglutide include: nausea, diarrhea, vomiting, constipation, stomach (abdomen) pain, changes in skin sensations, headache, tiredness (fatigue), upset stomach, dizziness, feeling bloated, belching, low blood sugar in people with type 2 diabetes, gas, stomach flu, heartburn, and hair loss.¹⁴

Novo is the global healthcare company that believes lasting health starts now. For over a century, we've combined leading scientific expertise with a deep understanding of people's lives. We develop treatments and support that help millions of people make progress they can see, feel and sustain now and in the future. Every day, over 66,500 employees around the world advance our purpose to drive change for lasting health. Through our partnerships, programs and investments, we're working to prevent disease, expand access to treatments and reduce our environmental impact to help even more people live healthier lives. In the United States, Novo has a 40-year presence, is headquartered in New Jersey and employs approximately 10,000 people. For more information, visit novonordisk.com and novonordisk-us.com and follow us on Instagram, LinkedIn, TikTok, Facebook, X and YouTube.

Contacts for further information

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References

1. Schattenberg JM, Armstrong MJ, Bakulin I, et al. Semaglutide improves liver health in non-obese participants with MASH: a post hoc analysis from the phase 3 ESSENCE trial. Presented at The Liver Meeting^® 2026; November 8, 2026; Denver, CO. Abstract 0072.
2. Sanyal AJ, Newsome PN, Kliers I, et al. Phase 3 trial of semaglutide in metabolic dysfunction-associated steatohepatitis. N Engl J Med. 2025;392(21):2089-2099.
3. Newsome PN, Sanyal AJ, Engebretsen KA, et al. Semaglutide 2.4 mg in participants with metabolic dysfunction-associated steatohepatitis: baseline characteristics and design of the phase 3 ESSENCE trial. Aliment Pharmacol Ther. 2024;60(11-12):1525-1533.
4. Allen AM, Charlton M, Cusi K, et al. Guideline-based management of metabolic dysfunction-associated steatotic liver disease in the primary care setting. Postgrad Med. 2024;136(3):229-245.
5. Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: a systematic review. Hepatology. 2023;77(4):1335-1347.
6. Estes C, Razavi H, Loomba R, Younossi Z, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 2018;67(1):123-133.
7. Quek J, Chan KE, Wong ZY, et al. Global prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in the overweight and obese population: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2023;8(1):20-30.
8. Miao L, Targher G, Byrne CD, Cao Y-Y, Zheng M-H. Current status and future trends of the global burden of MASLD. Trends Endocrinol Metab. 2024;35:697-707.
9. Muthiah MD, Cheng Han N, Sanyal AJ. A clinical overview of non-alcoholic fatty liver disease: a guide to diagnosis, the clinical features, and complications—What the non-specialist needs to know. Diabetes Obes Metab. 2022;24(Suppl 2):3-14.
10. Vanni E, Marengo A, Mezzabotta L, Bugianesi E. Systemic complications of nonalcoholic fatty liver disease: when the liver is not an innocent bystander. Semin Liver Dis. 2015;35(3):236-249.
11. Schattenberg JM, Lazarus JV, Newsome PN, et al. Disease burden and economic impact of diagnosed non-alcoholic steatohepatitis in five European countries in 2018: a cost-of-illness analysis. Liver Int. 2021;41(6):1227-1242.
12. Ekstedt M, Hagström H, Nasr P, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61(5):1547-1554.
13. Kugelmas M, Noureddin M, Gunn N, et al. The use of current knowledge and non-invasive testing modalities for predicting at-risk non-alcoholic steatohepatitis and assessing fibrosis. Liver Int. 2023;43(5):964-974.
14. Wegovy^® [package insert]. Plainsboro, NJ: Novo Nordisk Inc.

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