Survodutide Improves MASH Liver Endpoints Across Weight Loss Categories

Survodutide improved histologic and noninvasive liver endpoints in adults with metabolic dysfunction-associated steatohepatitis (MASH) and F2-F3 fibrosis across all weight reduction categories, including patients losing less than 5% of body weight, according to a post hoc analysis of a phase 2 trial presented at AASLD The Liver Meeting 2026.¹

Steatohepatitis-related endpoints rose more steeply with greater weight loss than fibrosis-related endpoints, which investigators suggested may reflect a direct hepatic effect of the glucagon receptor/glucagon-like peptide-1 (GLP-1) receptor dual agonist.¹

Arun Sanyal, MD, of Virginia Commonwealth University, presented the analysis. In the primary trial, 48 weeks of survodutide improved MASH without worsening of fibrosis in 47% to 62% of participants across doses, compared with 14% receiving placebo.2,3

How Did Liver Response to Survodutide Vary by Weight Loss?

The phase 2 trial randomized 295 adults with biopsy-confirmed MASH and F1-F3 fibrosis to once-weekly subcutaneous survodutide 2.4, 4.8, or 6.0 mg or placebo for 48 weeks.¹,² The current analysis included 170 participants with F2-F3 fibrosis and paired baseline and end-of-treatment biopsies, with survodutide doses pooled. Results were post hoc and descriptive, without confidence intervals.¹

Among 116 survodutide-treated participants, 16.4% (19) lost less than 5% of body weight, 29.3% (34) lost 5% to less than 10%, 22.4% (26) lost 10% to less than 15%, and 31.9% (37) lost 15% or more.¹ In comparison, 85.2% (46/54) of placebo-treated participants lost less than 5%.

MASH resolution without worsening of fibrosis occurred in 36.8%, 55.9%, 69.2%, and 78.4% of survodutide-treated participants across these categories, respectively.¹ Liver fat reductions of more than 30% by MRI proton density fat fraction followed a similar pattern, rising from 31.6% in the lowest category to 100% in the 2 highest categories.

Does Survodutide Improve Fibrosis Independent of Weight Loss?

Fibrosis improvement of at least 1 stage without worsening of MASH occurred in 47.4%, 41.2%, 53.8%, and 64.9% of survodutide-treated participants across weight reduction categories, a flatter gradient than seen for steatohepatitis endpoints.¹ A reduction of at least 0.5 in enhanced liver fibrosis (ELF) score occurred in 41.2% to 70.6%, and a liver stiffness reduction of more than 30% by FibroScan occurred in 36.8% to 78.4%.¹ A reduction of at least 20% in PRO-C3 occurred in 18.8%, 50.0%, 76.0%, and 58.8%, respectively.

Among participants losing less than 5% of body weight, survodutide outperformed placebo across liver endpoints.¹ In this group, MASH resolution occurred in 36.8% with survodutide vs 13.0% with placebo, fibrosis improvement in 47.4% vs 28.3%, and an ELF reduction of at least 0.5 in 41.2% vs 19.0%. Median alanine aminotransferase changed by −29.0% vs −5.2%, and aspartate aminotransferase by −31.9% vs 0.0%.¹

Investigators concluded improvements in steatohepatitis endpoints were largely associated with weight reduction, consistent with the metabolic drivers of MASH, while fibrosis-related improvements may be attributable to a direct hepatic effect of survodutide.¹

Survodutide is being evaluated in the phase 3 LIVERAGE trial in MASH with F2-F3 fibrosis and LIVERAGE-Cirrhosis in compensated MASH cirrhosis.

References:

1. Bugianesi E, Anstee QM, Lawitz E, et al. Efficacy of survodutide treatment assessed by liver endpoints across weight-reduction category at end of treatment: results from a phase 2 trial of survodutide in people with metabolic dysfunction-associated steatohepatitis and fibrosis. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.

2. Sanyal AJ, Bedossa P, Fraessdorf M, et al. A phase 2 randomized trial of survodutide in MASH and fibrosis. N Engl J Med. 2024;391(4):311-319. doi:10.1056/NEJMoa2401755

3. Brooks A. Survodutide improves MASH without worsening of fibrosis, reduces liver fat. HCPLive. Published June 7, 2024. Accessed November 7, 2026. https://www.hcplive.com/view/survodutide-improves-mash-without-worsening-of-fibrosis-reduces-liver-fat