One in every 5 people who have fatty liver disease have metabolic dysfunction-associated steatohepatitis (MASH), which was previously referred to as nonalcoholic steatohepatitis (NASH). People with MASH usually have a combination of disorders that increase their likelihood of fat buildup in the liver, such as diabetes, high cholesterol, and high blood pressure. This disorder can lead to significant problems like cirrhosis (severe scarring of the liver), liver cancer, and a need for a liver transplant.
Rezdiffra (resmetiron) was approved in 2024 and is the first medicine approved to treat NASH.
How Does It Work for NASH?
Rezdiffra belongs to a class of medicines called thyroid hormone receptor-beta (THR-β) agonists. In the liver, Rezdiffra attaches to the THR-β receptors. This attachment tells the liver to lower the amount of cholesterol that it makes, which eventually lowers the amount of fat in the liver.
How Do I Take It?
Rezdiffra comes as 60-milligram, 80-milligram, and 100-milligram tablets that you take by mouth once daily, with or without food. Rezdiffra should be used in combination with diet and exercise. When you take Rezdiffra for the first time, your dose will depend on how much you weigh. If you weigh less than 220 pounds, your dose will be 80 milligrams once daily. If you weigh 220 pounds or more, your dose will be 100 milligrams once daily. Certain other medicines may alter the blood levels of Rezdiffra. Your dose of Rezdiffra may need to be lower if you are taking one of these other medicines. Let your health care provider know of any medicines that you are taking before starting Rezdiffra. Take Rezdiffra as prescribed by your health care provider.
How Was Rezdiffra Studied for Treatment of NASH, and What Benefits Were Seen?
Rezdiffra was studied in a trial that included nearly 1,000 adults with NASH and severe liver scarring. They were told to take Rezdiffra or placebo pills (containing no medicine) once daily for a year. The dose used in the trial was either 80 milligrams or 100 milligrams. The average age of people in the trial was about 56, more than half were women (about 57%). Most of the people in the trial (about 90%) were White, about 2% of people in the study were Black, and 3% were Asian. Other races included in the study were not reported. Most people in the trial also had other diseases like high blood pressure, diabetes, and high cholesterol. The trial looked at two things to decide if Rezdiffra was helpful for improving NASH.
- Improvement of liver inflammation with no worsening of liver scarring
- Improvement of liver scarring with no worsening of liver inflammation
After a year of treatment, the study reported the following key results.
- Compared to the beginning of the study, liver inflammation went away (without increased liver scarring) in 14% to 23% more people who took Rezdiffra than those who took placebo pills.
- People who took Rezdiffra also had less liver scarring (without an increase in liver inflammation) compared to people who took placebo pills.
The study also found that Rezdiffra lowered low-density lipoprotein (LDL), or "bad" cholesterol, by about 15% over the study period.
Your results may differ from what was seen in clinical studies.
How Do I Manage Side Effects?
The most common side effects caused by Rezdiffra are diarrhea, nausea, itching, vomiting, constipation, stomach pain, and dizziness.
Eating small, more frequent meals may help to reduce nausea and vomiting while you are taking Rezdiffra. If you experience vomiting or diarrhea while taking Rezdiffra, make sure to drink plenty of fluids to stay hydrated. If you are constipated, eating more fiber can help. Many fruits and vegetables have high amounts of fiber, so increasing your intake of fruits and vegetables can help to keep you from getting constipated.
Dizziness can cause falls. If you get dizzy while taking Rezdiffra, avoid sudden head movements or getting up quickly from a sitting or lying position.
If you experience any side effects while taking Rezdiffra that do not improve or get worse, talk to your health care provider.
What Types of Drug Interactions Can Happen?
Several medicines can affect the blood levels of Rezdiffra.
Medicines called CYP2C8 inhibitors can increase the amount of Rezdiffra in the blood, which can increase the risk of side effects.
- Some CYP2C8 inhibitors, like gemfibrozil, can increase the amount of Rezdiffra in the blood by a lot. These medicines should not be taken while you are taking Rezdiffra.
- Other CYP2C8 inhibitors, like clopidogrel, can increase the amount of Rezdiffra by a smaller amount. Your health care provider may lower the dose of Rezdiffra if you are taking one of these CYP2C8 inhibitors.
Other medicines called OATP1B1 or OATP1B3 inhibitors can also increase the amount of Rezdiffra in the blood by a lot and should not be used while you are taking Rezdiffra.
- Cyclosporine is an OATP1B1/OATP1B3 inhibitor.
Rezdiffra can also increase the amount of other medicines in the blood, which can increase the risk of side effects from those other medicines.
- Rezdiffra increases the amount of certain statins in the blood. Atorvastatin (Atorvaliq, Lipitor), pravastatin, rosuvastatin (Crestor, Ezallor Sprinkle), and simvastatin (FloLipid, Zocor) are statin medicines, which are used to treat high cholesterol. When Rezdiffra is taken by someone who is also taking one of these statins, the combination can increase the risk for side effects from statins, like muscle pain and liver damage. If you are taking one of these statin medicines, your health care provider may need to lower your statin dose while you are taking Rezdiffra.
This is not a complete list of medicines that may interact with Rezdiffra. Tell your pharmacist or other health care provider about all the prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, or other supplements you take or have recently taken. This will help them determine if there are any interactions or if you need a dosage adjustment.
Is There Any Cost Assistance Available?
There is a savings card available from the drugmaker that may allow you to pay as little as $10 a month for the first year you are taking Rezdiffra. Whether you are eligible depends on your insurance coverage. You can find out more at portal.trialcard.com/madrigal/rezdiffra/landing or by calling 877-219-7770.
