GLP-1 Medications for the Treatment of Mast Cell Activation Syndrome (MCAS)

If you or someone you know lives with Mast Cell Activation Syndrome (MCAS), you know how unpredictable and exhausting it can be. This condition affects nearly every part of the body and can significantly impact everyday life. 

While the standard treatment options for MCAS improve and control symptoms for many people, some patients struggle to find treatment that works for them.

But now, new research is showing a promising new treatment option: GLP-1 receptor agonists. These medications have been found to help lower inflammation and regulate the immune system, which can significantly help people with MCAS.

In this blog, we'll review how MCAS is typically treated, what GLP-1 medications are, and how GLP-1 medications can help manage MCAS. But first, let's review exactly what MCAS is. 

What is Mast Cell Activation Syndrome (MCAS)?

MCAS is a condition that affects immune cells called mast cells. These mast cells act like the body's "alarm system." When they sense danger, like an infection, allergen, insect bite, or even stress, mast cells release chemical messengers all over the body to trigger inflammation and healing. These chemical messengers include:

  • Histamine

  • Prostaglandins

  • Cytokines

In someone without MCAS, the amount of these chemical messengers released is just enough to help the body fight off and heal from the infection, allergen, or other threat. However, in people with MCAS, their mast cells become overly sensitive and release these chemical messengers too easily or too often. 

Because these chemical messengers are released all throughout the body, MCAS symptoms often affect multiple body systems at once. These symptoms may include:¹

  • Brain/mood: Brain fog, depression, anxiety, memory difficulties, trouble concentrating

  • Skin: Hives, flushing, itching, angioedema (a potentially life-threatening allergic reaction that causes swelling of the deep layers of the skin

  • Sinuses: Itchy nose, stuffy nose, pink eye

  • Lungs/airway: Tightness of the throat or chest, difficulty breathing, wheezing

  • Heart: Low blood pressure, increased heart rate, palpitations, chest pain

  • Stomach/intestines: Nausea, abdominal pain, bloating, cramping, diarrhea

  • Muscles/bones: Pain

  • Body-wide: Fatigue, dysautonomia (dysfunction of the autonomic nervous system), anaphylaxis (a life-threatening allergic reaction)

For many people with MCAS, the symptoms are often debilitating and hard to control, making personalized treatment essential. 

How is MCAS Usually Treated?

Most people with MCAS are treated with a combination of medications and lifestyle changes to decrease mast cell activity and block chemical messengers. Here are of the most common treatments I start with:²

  • Antihistamines like cetirizine and famotidine work to decrease the effect of a chemical messenger called histamine

  • Mast cell stabilizers like cromolyn and ketotifen help regulate and stabilize mast cell functioning so they don't release as many chemical messengers

  • Leukotriene inhibitors like montelukast reduce other inflammatory chemicals that contribute to symptoms

Depending on the patient, lifestyle changes like stress reduction and low histamine diets can be helpful to manage symptoms. 

While these treatments often help, some patients continue to have flare-ups or persistent symptoms. In these cases, GLP-1 receptor agonists may be a good next step.

What are GLP-1 Medications?

GLP-1 medications are formally known as glucagon like peptide-1 receptor agonists. They work to mimic glucagon like peptide-1 (GLP-1), which is a hormone the body naturally produces to regulate appetite, blood sugar, and digestion. 

These medications were first developed for the treatment of type 2 diabetes and obesity, and they've become quite popular for this. Some of the most common GLP-1 medications include:³

  • Ozempic (Semaglutide)

  • Trulicity (Dulaglutide)

  • Victoza (Liraglutide)

  • Zepbound (Tirzepatide)

New research is showing that GLP-1 medications do more than help manage blood sugar and lower appetite. GLP-1 medications also have anti-inflammatory and immune-regulating effects.⁴ This finding is driving new research around GLP-1 medication use in patients with inflammatory, immune-driven conditions like MCAS. 

How is the Body Affected By GLP-1?

The key to understanding why GLP-1 medications help with MCAS comes down to the receptors these medications interact with. 

Every cell in the body has different receptors that determine how it responds to hormones and chemical messengers. These receptors vary depending on the function of that specific cell. Think of the receptor as a lock and the chemical messenger as the key.

Early research found that GLP-1 receptors were concentrated in the small intestine, pancreas, and the brain.⁵ This explains why GLP-1 medications work so well for treating type 2 diabetes and obesity. 

However, more recent research has shown that receptors for GLP-1 are found in cells all throughout the body, including mast cells.² This means that GLP-1, both natural and from GLP-1 medications, can influence immune and inflammatory responses throughout the body.

So what does this mean for people with MCAS? 

How GLP-1 Medications Help Manage MCAS

Several studies have now shown the different ways that GLP-1 medications help manage MCAS, and I've also seen promising improvements in my patients.

One 2025 study looked at 47 patients with MCAS who didn't respond to standard treatment and were started on a GLP-1 medication. What they found was that 89% of patients had a significant improvement in their symptoms—some within just 24 hours.² 

The reason for their symptom improvement is thought to be due to reduced mast cell activity, improved inflammation, improved gut health, nervous system protection, and regulated immune cell activity.

Let's dive into this.

1. GLP-1 Medications Calm Overactive Mast Cells

GLP-1 receptors on mast cells help control how easily the cells activate and release inflammatory chemicals. When these receptors are stimulated by GLP-1, mast cells are less likely to activate2 and release inflammatory chemicals like histamine.² 

This means less mast cell activation, fewer flares, and more controlled symptoms. 

2. GLP-1 Medications Lower Inflammation

GLP-1 medications have been shown to lower levels of several inflammatory chemicals largely because of their ability to regulate the immune system.⁶ The more the immune system reacts, the more inflammatory chemicals are released, and the more inflammation there is. 

These inflammatory chemicals are often seen in chronic inflammatory conditions like MCAS. But when the immune system is regulated and inflammation is reduced in patients with MCAS, many symptoms improve.

3. GLP-1 Medications Support Gut Health

Because of how GLP-1 medications slow digestion and strengthen the gut lining, GLP-1 medications help reduce "leaky gut" and digestive inflammation.⁷ These are both common triggers for MCAS symptoms. 

So by supporting the gut, GLP-1 medications may help lower immune reactivity, food-related flare ups, and uncomfortable digestive symptoms.

4. GLP-1 Medications Help to Protect the Nervous System

People with MCAS tend to have symptoms related to over activation of the nervous system. This includes symptoms like anxiety, dizziness, fatigue, or brain fog.

Early research showed that GLP-1 has effects on the central nervous system, which includes the brain and spinal cord.⁵ In a recent animal model, GLP-1s have shown to protect certain cells in the nervous system called neurons from harm by mast cells.⁸

Because of this, GLP-1 medications may help to stabilize the connection between the immune and nervous systems, which improves symptoms.

5. GLP-1 Medications Affect Other Immune Cells

GLP-1 medications not only affect mast cells. They also influence how other immune cells behave like T cells and macrophages, which are both types of white blood cells.⁹

These immune cells work alongside mast cells to fight off threats like infections. So if white blood cells like T cells and macrophages aren't working properly, they may be sending signals to mast cells causing them to over activate. 

So by regulating how these white blood cells work, mast cell activation may lessen, which can improve symptoms and reduce flares. 

Are You a Candidate for GLP-1 Treatment for MCAS?

If you have MCAS and haven't found relief with standard treatments, adding a GLP-1 medication may help improve your symptoms and quality of life. While more studies are ongoing, early results in research and in my own clinical practice are encouraging. 

If you're curious whether a GLP-1 medication might be a good option for you, I'd love to help.

With 22 years of experience treating patients with MCAS and other complex conditions, my goal is to help all of my patients find the safest, most effective path toward healing and feeling well again.

If you're ready to see if GLP-1 medications could help you, schedule an appointment with me below. 

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