Novo’s Wegovy® (semaglutide) reduced liver fat to normal levels in 9 out of 10 adults with obesity and excess liver fat – EASD2026

The liver findings come from an exploratory analysis rather than pre-specified primary or secondary trial endpoints.

Rhea-AI Summary

Novo Nordisk (NVO) presented an exploratory STEP UP analysis showing Wegovy reduced liver fat in adults with obesity without diabetes. In a 55-participant subgroup, mean liver fat with pooled injectable semaglutide 7.2 mg and 2.4 mg fell from 8.8% to 3.1% at week 72. Among 26 participants starting above 5% liver fat, 23 (88.5%) reached normal levels below 5%.

The broader analysis pooled 1,919 adults from STEP UP and STEP UP T2D. It was post hoc, meaning conducted after the trials, and liver measures were not pre-specified primary or secondary endpoints. Fewer than 1% met criteria for advanced liver-scarring risk at baseline. Semaglutide 2.4 mg is approved for MASH, an inflammatory fatty liver disease, in the United States, Canada, the United Kingdom, China and other markets; 7.2 mg is not being investigated for MASH. Novo expects part 2 results from its separate ESSENCE MASH trial in 2029.

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0 major · 4 points

Hollow bars mark forward-looking points. How the balance works

Positive

• Moderate pointSemaglutide 2.4 mg has MASH approval in the United States, Canada, United Kingdom, China and other markets.
• Moderate pointESSENCE showed superior liver-scarring improvement without worsening liver inflammation versus placebo at 72 weeks.
• Moderate pointESSENCE showed resolution of liver inflammation without worsening liver scarring versus placebo at 72 weeks.
• Minor pointLiver fat normalization reached 88.5% (23 of 26 participants) starting above 5% by week 72.
• Minor pointMean liver fat with pooled semaglutide doses declined from 8.8% to 3.1% at week 72.
• Minor point. Forward-looking: it has not happened yet and may not happen.ESSENCE part 2 results are expected in 2029.

Negative

• Minor pointLiver findings were post hoc and exploratory, not pre-specified primary or secondary trial endpoints.
• Minor pointDirect liver-fat measurements covered a subgroup of only 55 participants.
• Minor pointAdvanced liver-scarring risk criteria were met by fewer than 1% of participants at baseline.
• Minor pointSemaglutide 7.2 mg is not being investigated for MASH treatment.

Key Figures

Analyzed sub-population: 55 participants Mean liver fat: 8.8% at baseline to 3.1% at week 72 Reached normal liver fat threshold: 88.5% (23 participants)

Analyzed sub-population

55 participants

STEP UP post hoc analysis

Mean liver fat

8.8% at baseline to 3.1% at week 72

Semaglutide-treated group

Reached normal liver fat threshold

88.5% (23 participants)

Of 26 participants with baseline liver fat above 5%; below 5% by week 72

Key Terms

mri-pdff, fatty liver index (fli), fib-4 index, glp-1

4 terms

mri-pdff medical

"magnetic resonance imaging–proton density fat fraction (MRI-PDFF)"

MRI-PDFF (Magnetic Resonance Imaging-Proton Density Fat Fraction) is a medical imaging technique that measures the amount of fat within the liver or other tissues. For investors, it provides a precise way to assess health risks related to fat buildup, which can impact healthcare costs and the valuation of related companies. Its accuracy helps in monitoring treatment progress and predicting potential medical expenses, making it relevant for healthcare decision-making and investment considerations.

fatty liver index (fli) medical

"Fatty Liver Index (FLI)"

A fatty liver index (FLI) is a numerical score (0–100) that estimates the likelihood of hepatic steatosis (fat accumulation in the liver) using four routine measures: body mass index, waist circumference, blood triglycerides, and gamma‑glutamyl transferase (GGT). Higher values indicate greater probability of fatty liver; commonly used cutoffs are <30 to suggest fatty liver is unlikely and ≥60 to suggest fatty liver is likely. It is a noninvasive screening tool derived from statistical models and ultrasound comparisons, not a definitive diagnosis, and its accuracy can be affected by alcohol use, medications, ethnicity and other clinical factors.

fib-4 index medical

"FIB-4 index"

The FIB-4 index is a simple medical score that estimates the likelihood of liver fibrosis using four routinely measured values: age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. It is calculated by a standard formula that combines those inputs and produces a numeric result used to screen for and stratify risk of significant or advanced liver scarring; specific cutoffs classify low, indeterminate, or high probability of fibrosis. The score is a noninvasive triage tool—its accuracy can be affected by acute liver inflammation, age distributions, and certain medical conditions, so it indicates probability rather than providing a definitive diagnosis and is often followed by further testing when results are indeterminate or high.

glp-1 medical

"glucagon-like peptide-1 (GLP-1) receptor agonist"

GLP-1 (glucagon-like peptide-1) is a natural hormone in the body that helps regulate blood sugar levels and appetite. Its significance to investors lies in its role as the basis for a class of medications that address conditions like type 2 diabetes and obesity, which are large and growing markets. Advances or investments in GLP-1-based treatments can signal opportunities in healthcare innovation and potentially impact pharmaceutical companies’ growth.

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Novo reports analysis from STEP UP trial sub-population in which most participants with elevated liver fat achieved improved liver health after 72 weeks of Wegovy® (injectable semaglutide 7.2 and 2.4 mg) treatment.

• 9 in 10 achieved normal liver fat levels: Among participants with liver fat above 5%, 88.5% in the pooled group of people taking Wegovy® (injectable semaglutide 7.2 and 2.4 mg) achieved normal liver fat levels below 5% by week 72
• Liver fat was reduced by nearly two-thirds: Measures showed liver fat declined from 8.8% to 3.1% at week 72 with Wegovy®
• Wegovy® showed benefits in liver despite low baseline disease burden: Even participants with low baseline liver fat saw improvements in liver health with Wegovy® treatment
  

Bagsværd, Denmark, 1 October 2026 – Novo Nordisk today presented post hoc analysis of data from a STEP UP trial sub-population with 55 participants, showing that Wegovy® (pooled semaglutide 7.2 and 2.4 mg) reduced liver fat in adults with obesity without diabetes.¹ Change in percentage of liver fat, determined by magnetic resonance imaging (MRI), showed that mean liver fat in the group taking semaglutide declined from 8.8% at baseline to 3.1% at week 72. In addition, the analysis showed that 26 participants entered the trials with liver fat above 5% and 88.5% of them – 23 participants – reached the below-5% threshold by week 72, bringing their liver fat to normal levels. The findings are presented at the European Association for the Study of Diabetes (EASD) Annual Meeting 2026 in Milan, Italy.¹

“This analysis showed that semaglutide reduced liver fat and was linked to better overall liver health in adults with obesity,” said Eric Lawitz, MD, Texas Liver Institute and University of Texas Health San Antonio. “These findings suggest semaglutide may help address liver disease early – before it becomes a serious health problem – that could harm the heart, kidney, liver and metabolic health in the long term. This is important because as many as three in four people with obesity may have excess liver fat.“

What was the STEP UP pooled analysis of liver health?
The post hoc explorative analysis pooled 1,919 adults across STEP UP and STEP UP T2D, of whom 1,312 received semaglutide 7.2 mg, 304 received semaglutide 2.4 mg, and 303 received placebo.^2,3 At baseline, more than 94% of participants across all groups were classified as high risk for fatty liver by the Fatty Liver Index (FLI), while fewer than 1% met criteria for advanced fibrosis risk by the FIB-4 index. The population was therefore representative of individuals with obesity with high risk of metabolic dysfunction-associated steatohepatitis (MASH), but with low baseline burden of advanced liver disease.¹

A direct quantification of liver fat in the 55 participants with excess liver fat was determined by the non-invasive magnetic resonance imaging–proton density fat fraction (MRI-PDFF), which is the gold-standard imaging technique for quantifying hepatic steatosis.¹

“These findings help us look beyond the number on the scale and better understand the quality of the weight loss seen with semaglutide”, said Filip Knop, senior vice president and chief medical officer at Novo. “Our dedicated ESSENCE MASH trial demonstrated reversal of damage in the liver in people with MASH on semaglutide treatment, and this analysis from our STEP UP obesity trial reinforces semaglutide’s beneficial impact on liver health in people with obesity.”

Novo is investigating semaglutide 2.4 mg in MASH, and today it is approved for the treatment of MASH, under the brand name Wegovy®, in the United States, Canada, the United Kingdom, China and several other markets. Semaglutide 7.2 mg is not being investigated for the treatment of MASH.

About the STEP UP trial programme
STEP UP and STEP UP T2D were phase 3b randomised, double-blind, placebo-controlled trials evaluating semaglutide 7.2 mg once weekly versus semaglutide 2.4 mg and placebo for weight management.^2,3 STEP UP enrolled adults with obesity (BMI ≥30 kg/m²) without diabetes; STEP UP T2D enrolled adults with obesity and type 2 diabetes. The primary endpoints were change in body weight and proportion of participants achieving ≥5% weight loss at week 72.^2,3 The pooled analysis presented at EASD 2026 is a post hoc, exploratory analysis of liver-related indices and metabolic measures and was not a pre-specified primary or secondary endpoint of the parent trials.

About ESSENCE
ESSENCE is an ongoing phase 3 trial evaluating the effect of once-weekly injectable semaglutide 2.4 mg in people with MASH and moderate to advanced liver fibrosis (stage F2 or F3).   
The trial randomised 1,197 participants 2:1 to receive semaglutide 2.4 mg or placebo, on top of standard of care, for a total of 240 weeks.⁴ In part 1, the objective was to demonstrate that treatment with semaglutide 2.4 mg improved liver histology at 72 weeks based on biopsy sampling from the first 800 randomised patients. Semaglutide 2.4 mg led to superior improvement in liver fibrosis with no worsening of steatohepatitis, as well as resolution of steatohepatitis (removing fat, inflammation in liver cells and improving structural integrity of liver cells) with no worsening of liver fibrosis compared to placebo.⁴ Results from part 2 are expected in 2029. 

About semaglutide
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that mimics the effects of the naturally occurring hormone GLP-1, which regulates blood sugar and body weight. Semaglutide has been tested in several robust clinical development programmes and outcome studies in cardiometabolic diseases, including type 2 diabetes, obesity, cardiovascular disease, heart failure, chronic kidney disease, liver disease, and other related cardiometabolic diseases. Semaglutide is marketed under the brand names Wegovy® (injection or tablet), Ozempic® (injection or tablet), and Rybelsus® (tablet).

About MASLD and MASH
Metabolically-dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is characterised by excess fat accumulation in the liver and is strongly linked to obesity and type 2 diabetes. Left unaddressed, MASLD can progress to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, and cirrhosis.⁵ The Fatty Liver Index (FLI) is a validated non-invasive composite score using BMI, waist circumference, triglycerides, and gamma-glutamyl transferase (GGT) to estimate the risk of hepatic steatosis: values below 30 indicate “no fatty liver,” and values above 60 indicate “high risk.”⁶

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 67,000 employees around the world advance our purpose to drive change for lasting health. Through our partnerships, programmes 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. For more information, visit novonordisk.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
Christoffer Togo Solgaard-Tullin +45 3079 1471 cftu@novonordisk.com	Max Ung  +45 3077 6414  mxun@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. Lawitz E, Garvey WT, Jacobsen CSF, Quiroga M, Wilson L, Newsome PN. Effect of semaglutide on liver measures and indices: pooled analysis from the STEP UP trials. Abstract submitted to the European Association for the Study of Diabetes (EASD) Annual Meeting 2026.
2. Wharton S, Freitas P, Hjelmesæth J, et al. Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial. Lancet Diabetes Endocrinol. 2025;13(11):949–963. 
3. Lingvay I, Bergenheim SJ, Buse JB, et al. STEP UP T2D trial group. Once-weekly semaglutide 7.2 mg in adults with obesity and type 2 diabetes (STEP UP T2D): a randomised, controlled, phase 3b trial. Lancet Diabetes Endocrinol. 2025;13(11):935–948. 
4. 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;60:1525–1533.
5. Mary E Rinella, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023;78(6):1966-1986.
6. A Lum Han. Validation of fatty liver index as a marker for metabolic dysfunction-associated fatty liver disease. Diabetology & Metabolic Syndrome. 2022; 14:44.

Attachment

• PR261001-EASD-Wegovy-STEPUP

FAQ

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What did Novo Nordisk’s STEP UP analysis show about Wegovy and liver fat?

Mean liver fat with pooled semaglutide 7.2 mg and 2.4 mg declined from 8.8% at baseline to 3.1% at week 72. Among 26 participants whose initial liver fat exceeded 5%, 23 participants, or 88.5%, reached normal levels below 5%.

How were Novo Nordisk’s STEP UP liver-fat results measured?

Liver fat was measured using magnetic resonance imaging–proton density fat fraction, a non-invasive imaging method that quantifies fat in the liver. The broader pooled analysis also assessed liver-related indices and metabolic measures.

Who participated in Novo Nordisk’s pooled STEP UP liver analysis?

The pooled analysis included 1,919 adults: 1,312 received semaglutide 7.2 mg, 304 received semaglutide 2.4 mg and 303 received placebo. STEP UP enrolled adults with obesity without diabetes; STEP UP T2D enrolled adults with obesity and type 2 diabetes.

What is the design of Novo Nordisk’s ESSENCE MASH trial?

ESSENCE is an ongoing phase 3 trial of once-weekly injectable semaglutide 2.4 mg in people with MASH and moderate to advanced liver scarring. It randomized 1,197 participants 2:1 to semaglutide or placebo alongside standard care for 240 weeks. Part 1 assessed liver biopsies from the first 800 randomized patients at 72 weeks.