MASH Care Demands More Than New Drugs: Meena Bansal, MD

Two FDA-approved therapies and a rapidly expanding pipeline have fundamentally reshaped how clinicians approach metabolic dysfunction-associated steatohepatitis (MASH). However, a disease this complex, with consequences that ripple well beyond the liver, demands more than new drugs alone, explained Meena Bansal, MD, professor of medicine of liver diseases, system chief of the Division of Liver Diseases, and director of the MASLD/MASH Center of Excellence at the Icahn School of Medicine at Mount Sinai.

Semaglutide (Wegovy; Novo Nordisk) joined resmetirom (Rezdiffra; Madrigal Pharmaceuticals) as only the second approved treatment for patients with MASH and liver fibrosis after the FDA granted the glucagon-like peptide 1 (GLP-1) receptor agonist its approval in August 2025.^1,2 Resmetirom, a thyroid hormone receptor β–selective agonist, offers a liver-directed treatment for those with moderate to severe fibrosis without cirrhosis, while semaglutide has shown promise in resolving MASH and improving fibrosis.

In an interview with The American Journal of Managed Care^® (AJMC^®), Bansal, who presented multiple sessions at the European Association for the Study of the Liver (EASL) Congress, offered a candid assessment of where the field stands and where it still falls short. MASH, she explained, is no longer understood as simply a consequence of excess dietary fat but as a disease at the intersection of metabolic dysfunction, genetic susceptibility, gut-liver axis dysregulation, and systemic inflammation. That complexity demands a treatment paradigm that simultaneously addresses insulin resistance, cardiometabolic risk, and liver injury instead of single-target interventions.

Beyond these 2 agents, a pipeline of investigational therapies is expanding the horizon, including farnesoid X receptor (FXR) agonists and acetyl-CoA carboxylase (ACC) inhibitors, which each capture distinct pathophysiologic mechanisms. In addition, the dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonist tirzepatide and the dual GLP-1/glucagon receptor agonist survodutide have both been found to reduce liver fat and spark MASH improvement without worsening fibrosis.^3,4

Bansal identified the field's most consequential blind spots: the absence of therapies that robustly reverse cirrhosis, the lack of noninvasive biomarkers acceptable to the FDA as trial end points, and a persistent shortage of long-term cardiovascular outcomes data. Until emerging therapies can demonstrate reductions in cirrhosis, liver-related mortality, and cardiovascular events, she argued, the field's progress will remain incomplete.

AJMC: How has the understanding of MASH as a multifactorial disease changed the way clinicians need to approach treatment, and where does the field still fall short?

Bansal: MASH is now understood as a disease at the intersection of metabolic dysfunction, genetic susceptibility, gut-liver axis dysregulation, and systemic inflammation—not simply a consequence of excess dietary fat. This has shifted the treatment paradigm away from single-target interventions toward holistic, multidisciplinary management addressing insulin resistance, cardiometabolic risk, and liver injury simultaneously.

The field still falls short, however, in its ability to phenotype patients precisely enough to match them to the right therapy.

AJMC: There are several pipeline agents targeting different mechanisms—GLP-1s, FXR agonists, and ACC inhibitors. How do those approaches compare with current approved drugs, and do you expect them to complement or compete with those agents?

Bansal: Not all patients respond to any one therapy, suggesting that the primary driver of disease may vary among patients, justifying the need for drugs to work on multiple modes of action.

AJMC: Where do you see the biggest remaining gaps in the MASH therapeutic landscape, and what do you hope the next wave of data addresses?

Bansal: The most pressing gaps include the absence of therapies that robustly reverse cirrhosis, the lack of validated noninvasive biomarkers that can substitute for liver biopsy from an FDA perspective in trial end points and clinical monitoring, and insufficient data on long-term cardiovascular outcomes as primary end points in MASH trials. We need to ultimately see these emerging therapies translate into reductions in cirrhosis, liver-related mortality, and cardiovascular events.

References

1. Klein HE. FDA approves semaglutide for MASH with fibrosis. AJMC. August 18, 2025. Accessed May 28, 2026. https://www.ajmc.com/view/fda-approves-semaglutide-for-mash-with-fibrosis

2. Joszt L. FDA approves resmetirom, first treatment for NASH with liver fibrosis. AJMC. March 14, 2024. Accessed May 28, 2026. https://www.ajmc.com/view/fda-approves-resmetirom-first-treatment-for-nash-with-liver-fibrosis

3. Kaltwasser J. Weight loss, obesity drugs bring potential new MASLD, MASH treatment strategies. AJMC. April 16, 2026. Accessed May 28, 2026. https://www.ajmc.com/view/weight-loss-obesity-drugs-bring-potential-new-masld-mash-treatment-strategies