• In a real-world study, semaglutide 2.4 mg once weekly injection was associated with a statistically significant mean weight loss from baseline, 18.9 lb (8.6 kg; ~8%), when compared to resmetirom at six months
• Semaglutide 2.4 mg was also associated with significantly greater reductions than resmetirom in AST and some cardiometabolic measures
• Additional real-world data from a separate analysis found people initiating semaglutide 2.4 mg had greater one-year reductions in liver enzymes and weight, plus a larger HbA_1c decrease, versus those not initiating treatment with semaglutide 2.4 mg

PLAINSBORO, N.J. and BAGSVÆRD, Denmark, Nov. 6, 2026 /PRNewswire/ — Novo Nordisk today announced new real-world data from PLATINUM-Truveta and RHODIUM-2, which are two retrospective studies evaluating associations between semaglutide 2.4 mg once weekly injection use versus those not initiating treatment with semaglutide 2.4 mg and liver and cardiometabolic outcomes in adults with metabolic dysfunction-associated steatohepatitis (MASH). Results were presented at the American Association for the Study of Liver Diseases (AASLD), The Liver Meeting® 2026 in Denver, Colorado.

“Living with MASH can be incredibly challenging because the disease may progress without clear symptoms, making it even more important to understand the clinical data about how a treatment may help their disease,” said Michelle Skinner Moore, PhD, MBA, Vice President, Medical Affairs at Novo. “The findings from PLATINUM-Truveta and RHODIUM offer insights into real-world results for patients treated for MASH and help to inform providers.” 

PLATINUM-Truveta included 2,873 adults with MASH who initiated treatment with semaglutide 2.4 mg and 2,285 adults with MASH who initiated treatment with resmetirom. Key adjusted outcomes at three and six months are summarized below.¹

Table 1. Changes in liver enzymes & cardiometabolic markers from baseline to 3 months & 6 months from PLATINUM-Truveta

“Every patient with MASH has different metabolic needs,” said Dr. Eric Lawitz, Texas Liver Institute, and University of Texas Health San Antonio. “This real-world analysis offers insights that may help clinicians inform treatment decisions for people living with MASH.”

RHODIUM-2 compared 2,479 adults with MASH who initiated semaglutide 2.4 mg with 70,702 adults with MASH who did not initiate semaglutide. Key adjusted outcomes at 12 months are summarized below.²

Table 2. Change in liver enzymes and cardiometabolic markers from baseline to 12 months from RHODIUM-2*

Both studies were retrospective and observational. Treatment was not randomized, the groups differed in baseline characteristics, and results were based on patients with available follow-up measurements who met treatment-persistence criteria.

Real-world study data can provide valuable insights into how treatments work outside of controlled clinical trial settings. Real-world data analyses also have several limitations; while associations can be demonstrated, causal relationships cannot be definitively established. Results may reflect potential unmeasured confounding, the relatively recent approval of both treatments limited follow-up duration, and electronic medical record data may be subject to coding inaccuracies.

About PLATINUM-Truveta
PLATINUM-Truveta was an observational, retrospective cohort study that used de-identified electronic medical record data from the Truveta database across 30 US health systems from June 2021 through March 2026. Adults with MASH who initiated semaglutide 2.4 mg once weekly injection (n=2,873) or resmetirom (n=2,285) were included. Changes from baseline in ALT, AST, body weight, HbA_1c, platelets, triglycerides, HDL, and LDL were assessed at three and six months. Patients with prior use of semaglutide or resmetirom, cirrhosis or other chronic liver diseases were excluded, and treatment persistence was required at each time point. To reduce confounding, generalized estimating equations with inverse probability of treatment weighting were applied. Patients in the semaglutide group were defined as having MASH if they had one or more claims with a diagnosis code for MASH (ICD-10 CM K75.81) in the 12 month period before index date.¹

About RHODIUM-2
RHODIUM-2 was an observational, retrospective study that used de-identified electronic medical record data from the Truveta database across more than 30 US health systems from June 2021 through March 2026. Adults with MASH were grouped according to whether they initiated semaglutide 2.4 mg once weekly injection (n=2,479) or did not initiate semaglutide (n=70,702). Changes from baseline in ALT, AST, body weight, and HbA_1c were assessed at 3, 6, and 12 months. Patients with cirrhosis or other liver disease etiologies and those treated with GLP-1 receptor agonists or resmetirom within six months before start of first treatment were excluded. To control for confounding, generalized estimating equations to account for within patient correlation, and inverse probability of treatment weighting was applied.²

About metabolic dysfunction-associated steatohepatitis (MASH)
MASH is a serious, progressive, metabolic disease affecting the liver, which can be fatal if not managed properly.³ More than 250 million people live with MASH,⁴ and the number of individuals in advanced stages of the disease is expected to increase over 160% from 2015 to 2030.⁵ Of those living with overweight or obesity, more than one in three also have MASH.⁶ And of those currently living with MASH, more than 40% have type 2 diabetes, and more than 8 in 10 also live with obesity.⁷ People living with MASH often have many other health-related comorbidities,⁸ such as cardiovascular disease, which is the leading cause of death in people with MASH.^9,10

MASH is largely a silent disease due to few and unspecific symptoms in its early stages,³ where nearly 90% of people with MASH remain undiagnosed.¹¹ Once MASH progresses to late stages, there is increased mortality and morbidity, including potential for cirrhosis, liver cancer, and need for liver transplant.¹²

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.¹³ 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^†).¹³

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.¹³

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

References

1. Arora P, Shi D, Aly A, et al. Real-world comparative effectiveness of semaglutide versus resmetirom on liver enzymes and cardiometabolic markers in patients with MASH. Presented at The Liver Meeting® 2026; November 6, 2026; Denver, CO. Abstract 2461.
2. Albarmawi H, Shi D, Aly A, et al. Semaglutide 2.4 mg and the changes in liver enzymes and cardiometabolic markers in patients with MASH: a descriptive real-world data study. Presented at The Liver Meeting® 2026; November 6, 2026; Denver, CO. Abstract 2473.
3. 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.
4. Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023;77(4):1335-1347.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. Wegovy® [package insert]. Plainsboro, NJ: Novo Nordisk Inc.

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