Novo real-world studies link Wegovy® 2.4 mg to reductions in liver enzymes, weight, and blood sugar in adults with MASH at The Liver Meeting® (AASLD) 2026

The six-month comparison favored semaglutide for weight and blood sugar reductions, but resmetirom lowered LDL cholesterol more.

Rhea-AI Summary

Novo Nordisk (NVO) reported two observational studies linking Wegovy use to lower liver enzymes and weight in adults with MASH. MASH is metabolic dysfunction-associated steatohepatitis, a liver disease. In PLATINUM-Truveta, semaglutide 2.4 mg users lost 18.9 lb versus 5.6 lb with resmetirom at six months. Reductions in AST, a liver enzyme, and HbA1c, a blood sugar measure, were also greater; the difference in ALT, another liver enzyme, was not statistically significant. Resmetirom produced greater LDL cholesterol reductions.

In RHODIUM-2, semaglutide initiators lost 30.7 lb versus 2.4 lb among non-initiators at 12 months, alongside greater liver enzyme reductions. HbA1c fell 0.46 versus 0.09 percentage points. Both studies were retrospective and nonrandomized: baseline differences, follow-up selection and possible unmeasured confounding limit interpretation. The associations do not establish causation.

Positive

• Minor pointPLATINUM-Truveta weight reductions favored semaglutide: 10.5 versus 1.5 lb at three months; 18.9 versus 5.6 lb at six months.
• Minor pointPLATINUM-Truveta AST reductions favored semaglutide: 6.7 versus 1.9 U/L at three months; 10.4 versus 4.5 U/L at six months.
• Minor pointPLATINUM-Truveta HbA1c fell 0.29 percentage points with semaglutide versus a 0.03-point increase with resmetirom at three months.
• Minor pointPLATINUM-Truveta six-month HbA1c reductions favored semaglutide: 0.38 versus 0.08 percentage points.
• Minor pointPLATINUM-Truveta six-month platelet changes were +7.8 versus -4.4 for semaglutide versus resmetirom; P=0.022.

6 minor points

• Minor pointRHODIUM-2 twelve-month weight reductions were 30.7 versus 2.4 lb for semaglutide initiators versus non-initiators; P.
• Minor pointRHODIUM-2 twelve-month ALT reductions were 14.0 versus 3.8 U/L for semaglutide initiators versus non-initiators; P.
• Minor pointRHODIUM-2 twelve-month AST reductions were 9.1 versus 1.8 U/L for semaglutide initiators versus non-initiators; P=0.001.
• Minor pointRHODIUM-2 paired twelve-month HbA1c reductions were 0.46 versus 0.09 percentage points for semaglutide initiators versus non-initiators.
• Minor pointRHODIUM-2 elevated-ALT subgroup twelve-month ALT reductions were 24.3 versus 10.7 U/L for initiators versus non-initiators; P=0.002.
• Minor pointRHODIUM-2 elevated-ALT subgroup twelve-month AST reductions were 14.2 versus 5.3 U/L for initiators versus non-initiators; P=0.002.

Negative

• Minor pointBoth studies were retrospective and nonrandomized; observed associations cannot definitively establish causation.
• Minor pointBaseline differences, follow-up selection and treatment-persistence criteria create limitations on interpretation.
• Minor pointPossible unmeasured confounding, limited follow-up and electronic-record coding inaccuracies constrain the findings.
• Minor pointPLATINUM-Truveta LDL reductions favored resmetirom: 20.7 versus 10.3 at three months; 29.1 versus 13.7 at six months.
• Minor pointPLATINUM-Truveta ALT reductions showed no statistically significant between-group difference at three months or six months.

2 minor points

• Minor pointPLATINUM-Truveta triglyceride and HDL changes showed no statistically significant between-group differences at either time point.
• Minor pointPLATINUM-Truveta three-month platelet changes showed no statistically significant between-group difference.

Key Figures

Six-month body weight change: −18.9 lb vs. −5.6 lb 12-month body weight difference: −28.4 lb 12-month ALT difference: −10.5 U/L +3 more

Six-month body weight change

−18.9 lb vs. −5.6 lb

Semaglutide 2.4 mg vs. resmetirom; between-group p<0.001

12-month body weight difference

−28.4 lb

Adjusted between-group difference in RHODIUM-2

12-month ALT difference

−10.5 U/L

Adjusted between-group difference in RHODIUM-2; p<0.01

12-month AST difference

−7.3 U/L

Adjusted between-group difference in RHODIUM-2; p=0.001

12-month HbA1c change

−0.46 vs. −0.09 percentage points

Semaglutide initiators vs. no initiation; between-group difference not reported

RHODIUM-2 cohort size

2,479 vs. 70,702 adults

Semaglutide initiators vs. adults who did not initiate semaglutide

Key Terms

hba1c, generalized estimating equations, inverse probability of treatment weighting

3 terms

hba1c medical

"Changes in liver enzymes & cardiometabolic markers"

A1c (HbA1c) is a blood test that measures how much sugar has stuck to red blood cells over the past two to three months, giving a single number that reflects average blood glucose control—think of it as a running average score for blood sugar. Investors watch A1c because it’s a common clinical measure used to judge whether diabetes drugs, devices or care programs work, influence regulatory approvals, treatment guidelines and market demand.

generalized estimating equations technical

"generalized estimating equations with inverse probability of treatment weighting"

A statistical method for analyzing correlated or repeated-measures data that produces estimates of average (population-level) relationships while accounting for within-subject or within-cluster similarity. Generalized estimating equations (GEE) fit a regression model for the mean response and use a “working” correlation structure to model how observations within the same subject or cluster are related; coefficient estimates are consistent even if that correlation is misspecified, though estimated standard errors and efficiency can be affected. GEE yields population-averaged effects rather than subject-specific trajectories and is commonly used for longitudinal, clustered, or repeated binary, count, or continuous outcomes.

inverse probability of treatment weighting technical

"inverse probability of treatment weighting was applied"

A statistical method used in observational studies to estimate the effect of a treatment or exposure by weighting each subject by the inverse of their probability of receiving the treatment they actually received (their propensity score). Weighting creates a synthetic sample in which measured baseline characteristics are balanced across treatment groups, so differences in outcomes can be attributed to the treatment under the assumption that all confounders are measured and the propensity model is correctly specified; if those assumptions fail, the estimates can be biased.

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• 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

Time point and measure	Semaglutide 2.4 mg	Resmetirom	Between-group P value
Three months
AST (U/L)	-6.7	-1.9	<0.001
ALT (U/L)	-8.7	-4.8	0.077
HbA1c (percentage points)	-0.29	+0.03	<0.001
Body weight (lb)	-10.5	-1.5	<0.001
Triglycerides	-27.9	-26.0	0.83
HDL	-2.0	-0.7	0.34
LDL	-10.3	-20.7	<0.05
Platelets	+6.8	+2.7	0.48
Six months
AST (U/L)	-10.4	-4.5	<0.001
ALT (U/L)	-14.8	-11.6	0.20
HbA1c (percentage points)	-0.38	-0.08	<0.001
Body weight (lb)	-18.9	-5.6	<0.001
Triglycerides	-29.4	-30.5	0.91
HDL	+0.3	-1.4	0.29
LDL	-13.7	-29.1	<0.001
Platelets	+7.8	-4.4	0.022

ALT = alanine aminotransferase; AST = aspartate aminotransferase; HDL = high-density lipoprotein; LDL = low-density lipoprotein. Values are adjusted mean changes from baseline. Negative values indicate reductions. Values presented are weighted means without additional covariate adjustment.

"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*

Measure	Semaglutide 2.4 mg  initiators	No semaglutide initiation	Adjusted between-group difference	P value
ALT (U/L)	-14.0	-3.8	-10.5	<0.01
AST (U/L)	-9.1	-1.8	-7.3	0.001
Body weight (lb)	-30.7	-2.4	-28.4	<0.001
HbA1c (percentage points)*	-0.46	-0.09	NR	NR
Exploratory endpoints
Elevated ALT subgroup — ALT (U/L)	-24.3	-10.7	-13.7	0.002
Elevated ALT subgroup — AST (U/L)	-14.2	-5.3	-8.9	0.002

Values are adjusted mean changes from baseline, except HbA1c. Negative values indicate reductions. NR = not reported. Elevated ALT defined as ALT > 25 in women and ALT > 35 in men. *The results are paired baseline and 12-month data.

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

Novo Media:
Ambre James-Brown +45 3079 9289 globalmedia@novonordisk.com	Liz Skrbkova (US) +1 609 917 0632 USMediaRelations@novonordisk.com
Novo Investors:
Michael Novod +45 3075 6050 nvno@novonordisk.com	Sina Meyer +45 3079 6656 azey@novonordisk.com
Max Ung +45 3077 6414 mxun@novonordisk.com	Christoffer Togo Solgaard-Tullin +45 3079 1471 cftu@novonordisk.com
Ida Schaap Melvold +45 3077 5649 idmg@novonordisk.com	Mads Berner Bruun +45 3075 2936 mbbz@novonordisk.com
Frederik Taylor Pitter (US) +1 609 613 0568 fptr@novonordisk.com	Alex Bruce (US) +1 640 230 0276 axeu@novonordisk.com

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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FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

Who was included in Novo Nordisk's PLATINUM-Truveta and RHODIUM-2 MASH studies?

PLATINUM-Truveta included 2,873 adults initiating semaglutide 2.4 mg and 2,285 initiating resmetirom; RHODIUM-2 included 2,479 semaglutide initiators and 70,702 non-initiators. Both used electronic medical records covering June 2021 through March 2026 and excluded patients with cirrhosis or other liver diseases.

Is Novo Nordisk's semaglutide 2.4 mg approved for MASH?

Semaglutide 2.4 mg has FDA accelerated approval for adults with MASH and moderate-to-advanced liver scarring, but not cirrhosis, alongside a reduced-calorie diet and increased physical activity. Continued approval may depend on verification of clinical benefit in a confirmatory trial. Novo Nordisk is investigating the treatment in the ongoing ESSENCE phase 3 trial.