PPAR Alpha/Delta Agonists

PPAR agonists are a treatment option for primary biliary cholangitis (PBC). They are only used when ursodeoxycholic acid (UDCA) does not work well. Over half of people with PBC respond well to PPAR agonists.¹

This article covers how PPAR agonists are used to treat PBC. It also explains possible side effects. Talk to your doctor about the risks and benefits of PPAR agonists.

How do PPAR agonists work?

PPAR stands for “peroxisome proliferator-activated receptor.” It is a family of proteins that turn your genes on and off. PPAR regulates metabolism, fat and sugar balance, and inflammation. There are several PPAR types:²

• PPAR alpha – mostly in the liver and involved in bile acid balance
• PPAR beta/delta – found in many tissues and involved in fat metabolism
• PPAR gamma – involved in fat and glucose metabolism

Drugs that activate PPAR are called PPAR “agonists.” They target 1 or more types of PPAR. Experts do not know exactly how PPAR agonists treat PBC. They may reduce how much bile acid your body makes.^1,2

PPAR agonists may be combined with UDCA or used alone. After 1 year of treatment, PPAR agonists improve liver function for over half of people with PBC. We do not yet know if they prevent liver scarring or improve survival rates.^1,3

Examples of PPAR agonists

In 2024, the US Food and Drug Administration (FDA) approved 2 PPAR agonists to treat PBC:^4,5

• Elafibranor (Iqirvo™) – targets PPAR alpha and PPAR delta
• Seladelpar (Livdelzi™) – targets PPAR delta

Other PPAR agonists are approved to treat other conditions, like hyperglyceridemia. We need more research on their benefits in PBC. But doctors may prescribe them “off-label” to treat PBC. These include the fibrates:^1,3,6

• Fenofibrate (Tricor™, Lipofen™, others) – targets PPAR alpha
• Bezafibrate (Bezalip™) – targets all PPAR types
• Ciprofibrate (Lipanor™, Modalim™, others) – targets PPAR alpha

What are the possible side effects of PPAR agonists?

Side effects vary depending on the PPAR agonist. Side effects of PPAR agonists are usually mild. The most common side effects of PPAR agonists include:^4,5

• Weight gain or weight loss
• Diarrhea or constipation
• Abdominal pain or swelling
• Headache or dizziness
• Nausea and vomiting
• Joint pain or stiffness
• Stomach pain
• Gastroesophageal reflux disease (GERD)
• Dry mouth
• Rash

PPAR agonists may cause serious side effects. These include:^4,5

• Severe muscle pain
• Bone fractures
• Liver problems
• Allergic reactions
• Gallstones

Before and during treatment, your doctor will perform tests. They may monitor you for muscle problems and other side effects. This can help make decisions about treatment.^4,5

These are not all the possible side effects of PPAR agonists. Talk to your doctor about what to expect when taking PPAR agonists. Call your doctor if you notice any changes that concern you.

Other things to know about PPAR agonists

Take PPAR agonists as your doctor prescribes. They are usually taken as oral tablets once a day. You may take PPAR agonists with or without food.^4,5

Before starting treatment for PBC, tell your doctor about all your health conditions. People with signs of advanced liver disease should not take PPAR agonists.^4,5

Talk to your doctor about any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs. PPAR agonists can affect how other drugs work. Other drugs can also affect how PPAR agonists work.^4,5

Talk to your doctor if you are pregnant or plan to become pregnant. Some PPAR agonists can harm an unborn baby. Some can also reduce how well hormonal contraceptives work. Talk to your doctor about preventing pregnancy during treatment.^4,5

Researchers are continuing to study PPAR agonists. They are testing whether PPAR agonists prevent liver scarring or improve survival rates. Researchers are also studying new PPAR agonists. This includes saroglitazar, which targets PPAR alpha and PPAR gamma.¹