What is a MASH Drug? Understanding Treatments for Metabolic Dysfunction-Associated Steatohepatitis

October 7, 2025 •

3 min read

In 2024, the U.S. Food and Drug Administration (FDA) approved the first-ever drug for Metabolic Dysfunction-Associated Steatohepatitis (MASH), a serious liver disease. A MASH drug is a medication specifically designed to treat this condition, which is characterized by fat buildup, inflammation, and scarring in the liver. The approval of these specialized treatments marks a significant advancement for millions affected by this progressive disease, who previously had limited therapeutic options.

Quick Summary

A MASH drug is a therapeutic agent used for metabolic dysfunction-associated steatohepatitis (MASH), a progressive form of fatty liver disease. These medications target the inflammation and fibrosis caused by fat buildup in the liver. Recent regulatory approvals have introduced the first specific drug therapies for this condition, which previously lacked approved pharmaceutical treatments.

Key Points

MASH is a Severe Liver Condition: MASH is Metabolic Dysfunction-Associated Steatohepatitis, a progressive liver disease involving fat buildup, inflammation, and scarring.
MASH Drugs Treat the Underlying Pathology: Unlike general weight loss or diabetes drugs, MASH drugs target the specific metabolic pathways driving liver damage.
Resmetirom is the First Approved MASH Drug: Approved in March 2024, resmetirom (Rezdiffra) is the first FDA-approved medication for MASH with moderate to advanced fibrosis.
Several Drug Classes are Being Developed: In addition to THR-β agonists like resmetirom, other drug types like GLP-1 agonists and FGF21 analogues are being developed or repurposed for MASH treatment.
Not a Slang Term: The medical term 'MASH drug' is not related to the slang term for being intoxicated; it refers exclusively to medication for the liver disease.
Lifestyle Changes are Still Important: MASH drugs are meant to be used in combination with diet and exercise, which remain critical components of managing the disease.
New Nomenclature: The term MASH replaced NASH (non-alcoholic steatohepatitis) in 2023 to provide a more accurate and less stigmatizing diagnosis.

Understanding Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Before exploring what a MASH drug does, it is important to understand the disease it treats. MASH, which stands for Metabolic Dysfunction-Associated Steatohepatitis, was previously known as Non-Alcoholic Steatohepatitis (NASH) until a 2023 international consensus renamed it. This was done to provide a more accurate and less stigmatizing name for a condition that affects millions globally.

MASH is a severe form of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), a general term for having excessive fat in the liver. In MASH, this leads to inflammation, liver cell damage, and potentially fibrosis (scarring), which can advance to cirrhosis, liver failure, or liver cancer.

MASH is closely linked to metabolic syndrome risk factors such as obesity, type 2 diabetes, and high cholesterol. Symptoms are often absent in early stages, highlighting the need for targeted therapies.

How MASH Drugs Work: Mechanisms of Action

Historically, managing MASH relied on lifestyle modifications like diet and exercise, which were often insufficient to reverse advanced fibrosis. MASH drugs represent a new treatment approach by targeting the metabolic pathways underlying the disease. Several types are being developed or are available:

Thyroid Hormone Receptor-β (THR-β) Agonists: These drugs activate THR-β receptors in the liver, reducing liver fat, inflammation, and fibrosis.
GLP-1 Agonists: Known for use in diabetes and weight loss, these drugs like semaglutide can also improve liver metabolism, reducing fat and inflammation.
FGF21 Analogues: These agents mimic the hormone FGF21, which regulates metabolism, to improve metabolic dysfunction in MASH.

The First FDA-Approved MASH Drug: Resmetirom (Rezdiffra)

Resmetirom (Rezdiffra) was approved by the FDA in March 2024 as the first specific MASH medication. This oral THR-β agonist targets liver pathways to address the disease's core issues. It's approved for adults with MASH and moderate to advanced liver scarring (fibrosis stages 2 and 3), in conjunction with diet and exercise. Clinical trials showed resmetirom could resolve MASH and/or improve liver fibrosis.

Comparison of MASH Drug Types


Drug Type	Mechanism of Action	Examples	FDA Approval for MASH	Use Case
Thyroid Hormone Receptor-β Agonists	Selectively activates THR-β receptors in the liver to reduce fat and inflammation.	Resmetirom (Rezdiffra)	Yes (Resmetirom, March 2024)	Adults with MASH and moderate to advanced liver fibrosis.
GLP-1 Agonists	Improves metabolism, reduces inflammation, and promotes weight loss.	Semaglutide (Wegovy), Tirzepatide	Yes (Wegovy, August 2025)	MASH with moderate-to-advanced fibrosis; also used for obesity and diabetes.
FGF21 Analogues	Mimics FGF21 hormone to regulate metabolic processes; aims to reduce inflammation and fibrosis.	Efruxifermin (in trials)	No (currently in clinical trials)	Still in development; potential for future MASH treatment.

Other Considerations and Ongoing Research

The MASH treatment field is developing rapidly following resmetirom's approval. Other drugs with different mechanisms, like lanifibranor and survodutide, are in clinical trials. Research is exploring combination therapies, especially for advanced disease.

It's important to distinguish the medical term MASH drug from the slang term, which refers to being under the influence of recreational drugs. Medically, it specifically pertains to liver disease treatment. Patients with MASH should also avoid alcohol entirely to prevent worsening liver damage.

Conclusion

A MASH drug is a targeted medication for Metabolic Dysfunction-Associated Steatohepatitis. The FDA's approval of resmetirom provides a specific treatment option for patients with advanced liver fibrosis, complementing lifestyle changes. The field is evolving with new drug candidates and strategies, offering hope for those with this metabolic disorder. These new treatments represent a significant shift toward pharmacologically specific management of MASH. For further information and resources, you can visit the official website of Madrigal Pharmaceuticals.

Frequently Asked Questions

In a medical context, MASH stands for Metabolic Dysfunction-Associated Steatohepatitis. It is a serious form of liver disease characterized by inflammation and cell damage caused by fat buildup.

Yes, a MASH drug is essentially the same as what was previously called a NASH drug. The medical community formally renamed the condition from Nonalcoholic Steatohepatitis (NASH) to MASH in 2023 to update the terminology.

The first FDA-approved MASH drug is resmetirom, marketed under the brand name Rezdiffra. It was approved in March 2024 for adults with MASH who have moderate to advanced liver scarring.

MASH drugs work by targeting the metabolic issues that cause liver damage. For example, resmetirom, a thyroid hormone receptor-β agonist, reduces liver fat accumulation, inflammation, and scarring by acting on specific receptors in the liver.

Resmetirom is approved for adults diagnosed with MASH who have moderate to advanced liver fibrosis (stage 2 or 3). Eligibility is determined by a healthcare provider, and a liver biopsy is not always required for diagnosis.

While lifestyle changes like diet and exercise can improve liver health and sometimes reverse fatty liver disease, they may not be sufficient to reverse the advanced fibrosis seen in MASH. Medications are a critical new tool, especially for patients with significant scarring.

Yes, many other drugs are in various stages of clinical trials. These include GLP-1 agonists like semaglutide (also used for obesity and diabetes) and FGF21 analogues, all aiming to reduce liver inflammation and fibrosis.