Semaglutide Linked to Lower Liver Enzymes, Weight in Real-World MASH Data

Semaglutide 2.4 mg (Wegovy) was associated with reductions in liver enzymes, body weight, and glycated hemoglobin (HbA1c) in adults with metabolic dysfunction-associated steatohepatitis (MASH) treated in routine practice, according to 2 retrospective real-world analyses presented at The Liver Meeting 2026.¹

Novo Nordisk announced the findings on November 6, 2026, including a comparison of semaglutide with resmetirom (Rezdiffra) and a comparison with patients who did not initiate semaglutide.¹

"Every patient with MASH has different metabolic needs," Eric Lawitz, MD, Texas Liver Institute, and University of Texas Health San Antonio, said in a statement.¹ "This real-world analysis offers insights that may help clinicians inform treatment decisions for people living with MASH."

The US Food and Drug Administration granted semaglutide 2.4 mg accelerated approval in August 2025 for adults with noncirrhotic MASH and moderate to advanced fibrosis (F2–F3), based on 72-week histologic results from the phase 3 ESSENCE trial. In the trial, 63% of patients receiving semaglutide achieved steatohepatitis resolution without worsening of fibrosis, compared with 34% receiving placebo.^2,3

How Did Semaglutide Compare With Resmetirom in PLATINUM-Truveta?

PLATINUM-Truveta used deidentified electronic health record data from 30 US health systems in the Truveta database between June 2021 and March 2026.¹ The analysis compared adults with MASH initiating semaglutide 2.4 mg (n = 2873) or resmetirom (n = 2285), excluding patients with prior use of either agent, cirrhosis, or other chronic liver disease. Investigators used generalized estimating equations with inverse probability of treatment weighting, and patients were required to remain on treatment at each time point.¹

At 6 months, semaglutide was associated with a greater reduction in aspartate aminotransferase (AST) than resmetirom (−10.4 vs −4.5 U/L; P < .001).¹ Alanine aminotransferase (ALT) reductions did not differ significantly between groups (−14.8 vs −11.6 U/L; P = .20). Semaglutide was also associated with greater reductions in body weight (−18.9 vs −5.6 lb; P < .001) and HbA1c (−0.38 vs −0.08 percentage points; P < .001).¹

Lipid findings were mixed. LDL cholesterol declined more with resmetirom than semaglutide at 6 months (−29.1 vs −13.7; P < .001), while triglyceride and HDL cholesterol changes were similar between groups.¹ Platelet counts increased with semaglutide and decreased with resmetirom (+7.8 vs −4.4; P = .022).

What Did RHODIUM-2 Show at 12 Months?

RHODIUM-2 drew on Truveta data from more than 30 US health systems over the same period, comparing adults with MASH who initiated semaglutide 2.4 mg (n = 2479) with those who did not (n = 70,702).¹ Patients with cirrhosis, other liver disease etiologies, or recent glucagon-like peptide-1 (GLP-1) receptor agonist or resmetirom use were excluded.

At 12 months, semaglutide initiators had greater reductions in ALT (−14.0 vs −3.8 U/L; adjusted difference, −10.5; P < .01) and AST (−9.1 vs −1.8 U/L; adjusted difference, −7.3; P = .001) than noninitiators. Body weight declined by 30.7 lb with semaglutide vs 2.4 lb without (adjusted difference, −28.4 lb; P < .001), and HbA1c fell by 0.46 vs 0.09 percentage points.¹

In an exploratory subgroup with elevated baseline ALT, defined as more than 25 U/L in women and more than 35 U/L in men, semaglutide was associated with an adjusted ALT difference of −13.7 U/L (P = .002) and an adjusted AST difference of −8.9 U/L (P = .002).¹

Novo Nordisk noted both studies were retrospective and observational, with baseline differences between groups, short follow-up, and potential residual confounding and coding errors.¹ The analyses included only patients with follow-up measurements who met persistence criteria, and the release did not report fibrosis measures, confidence intervals, or safety data. Part 2 of ESSENCE, evaluating liver-related clinical outcomes at 240 weeks, is ongoing.²

References:

1. Novo Nordisk. 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. PR Newswire. Published November 6, 2026. Accessed November 6, 2026. https://www.prnewswire.com/news-releases/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--302932360.html

2. Brooks A. FDA approves semaglutide (Wegovy) injection 2.4 mg for noncirrhotic MASH. HCPLive. Published August 15, 2025. Accessed November 6, 2026. https://www.hcplive.com/view/fda-approves-semaglutide-wegovy-injection-2-4-mg-for-noncirrhotic-mash

3. Brooks A. ESSENCE: semaglutide improves fibrosis, resolves steatohepatitis in MASH. HCPLive. Published November 1, 2024. Accessed November 6, 2026. https://www.hcplive.com/view/essence-semaglutide-improves-fibrosis-resolves-steatohepatitis-in-mash