Medications for Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Metabolic dysfunction-associated steatohepatitis (MASH) is a condition in which there is liver inflammation and damage caused by fat buildup in the liver. It is the more severe form of metabolic dysfunction-associated steatotic liver disease (MASLD), and it can lead to complications such as cirrhosis and liver failure if left untreated. Fortunately, there are medicines available to help manage MASH and reduce the risk that it will get worse.¹

The medicines you take for MASH depend on several things:^1,2

• Your existing liver function, or how well your liver is working
• The stage of your liver damage
• Other health conditions (comorbidities) that affect your liver

Goals of treating MASH

The primary goals of treating MASH are to:²

• Reduce liver inflammation
• Prevent further liver damage
• Improve overall liver health

Achieving these goals can help slow down or even reverse the progression of the disease. This reduces the risk of associated health problems (complications) and improves quality of life.^1,2

For many people, losing excess weight can make a big difference in fatty liver outcomes. Until recently, it was the only recommended treatment for MASH.^1,2

Medicines for liver scarring (fibrosis)

For those with liver scarring (fibrosis) due to MASH, there is now a medicine approved to treat it. This drug is called Rezdiffra™ (resmetirom). Rezdiffra is approved by the US Food and Drug Administration (FDA) to treat people with MASH who have moderate to severe liver scarring. It is meant to be taken along with a modified diet and exercise plan.³

Rezdiffra may interact with other medicines, particularly statins. Talk to your doctor about whether this drug is right for you.³

Medicines for high blood sugar

High blood sugar, a hallmark feature of type 2 diabetes, is commonly linked to MASH. In fact, type 2 diabetes is a common comorbidity of MASH. High blood sugar puts extra stress on the liver, and it can contribute to liver damage.^4-7

Medicines that help lower blood sugar levels can be helpful in managing MASH. Slowing down liver damage for people with diabetes can be achieved with a few different types of medicines.^4-7

Metformin

Since the 1950s, metformin has been a first-line treatment for type 2 diabetes. Because of its positive effects on blood sugar, weight management, and reduction of fat buildup, it has been used more recently in the treatment of people with MASLD and MASH.⁴

Studies have shown that metformin can help reduce fat buildup in the liver and help with weight loss. It may even be beneficial for those with fibrosis and cirrhosis.⁴

However, other studies have shown no effect of using the drug for MASH. And there is some evidence that the drug may have negative effects on people with advanced liver disease, such as cirrhosis. More research on the use of metformin for those with advanced liver disease like MASH is needed.⁴

Pioglitazone

Pioglitazone is a medicine that improves insulin sensitivity and can help reduce liver inflammation in people with MASLD and MASH. But some studies show that the drug may cause weight gain. Bladder cancer may be another side effect of the drug.^4,5

Glucagon-like peptide 1 (GLP-1) receptor agonists

GLP-1 receptor agonists, or GLP-1 RAs, are a class of medicine that can help lower blood sugar levels. These medicines can also help in weight loss and have been shown to decrease the scar tissue in the liver associated with MASH.^4,6

Examples of GLP-1 RAs include:⁶

• Dulaglutide (Trulicity®)
• Exenatide (Byetta®)
• Exenatide extended-release (Bydureon®)
• Liraglutide (Victoza®)
• Lixisenatide (Adlyxin®)
• Semaglutide injection (Ozempic®, Wegovy®)
• Semaglutide tablets (Rybelsus®)

Sodium-glucose cotransporter-2 (SGLT2) inhibitors

Sodium-glucose cotransporter-2 (SGLT2) inhibitors help control blood sugar. They are often prescribed for people with type 2 diabetes. Research shows that they are helpful for people with MASLD and MASH, even if the person does not have diabetes.^4,7

Examples of SGLT2 inhibitors your doctor might prescribe to control your blood sugar include:⁷

• Dapagliflozin (Farxiga®)
• Canagliflozin (Invokana®)
• Empagliflozin (Jardiance®)
• Ertugliflozin (Steglatro®)

Medicines for high cholesterol

High cholesterol levels are another common feature of MASH and can contribute to liver damage and heart disease.²

Statins

Statins are a class of medicine often used to lower cholesterol levels and reduce the risk of heart disease. Statins have also been shown to reduce inflammation in the body and have anti-scarring effects. This can be helpful for those with MASLD and MASH.⁸

While there have been no clinical trials explicitly testing statins’ role on MASH yet, analysis from other studies has shown that it does seem to have a positive effect on the features of MASH (fat buildup in the liver and scarring in the liver).⁸

Some examples of statins are:⁸

• Atorvastatin (Lipitor®)
• Fluvastatin
• Rosuvastatin (Crestor®)
• Pravastatin
• Simvastatin (Zocor®)

Medicines for high blood pressure

High blood pressure is often linked with liver damage and MASH. When you have high blood pressure, it is important to manage it with medicines to decrease your risk of liver damage and heart complications. Many types of drugs may be prescribed to treat blood pressure.^9,10

Angiotensin-converting enzyme (ACE) inhibitors

These drugs reduce blood pressure. They do this by blocking hormones that constrict blood vessels. They have also been shown to reduce fibrosis.¹¹

Examples of ACE inhibitors include:¹²

• Lisinopril (Zestril®)
• Enalapril (Vasotec®)
• Perindopril (Coversyl®)
• Ramipril (Altace®)

Angiotensin receptor blockers (ARBs)

These drugs lower blood pressure by widening blood vessels. ARBs are often used to manage high blood pressure, diabetic nephropathy (diabetes-related kidney damage), and hypertensive heart disease. Recent research shows they could also be helpful for people with MASLD and MASH, especially those who have had a liver transplant.¹³

Examples of ARBs include:¹³

• Losartan (Cozaar®)
• Valsartan (Diovan®)
• Irbesartan (Avapro®)

Understanding your medicines

Before beginning treatment for MASH, be sure you understand what the medicine does and how to take it. Tell your doctor or healthcare team if you have any questions or concerns.

Also, be sure to tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs.