Case Series Suggests Potential Role for GLP-1 Receptor Agonists in MCAS
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) demonstrated potential clinical benefit in patients with mast cell activation syndrome (MCAS) in a case series evaluating their use in refractory disease.
MCAS is characterized by inappropriate mast cell activation with little or no neoplastic mast cell proliferation, distinguishing it from mastocytosis. The disorder is associated with substantial biologic heterogeneity, driven in part by diverse mast cell regulatory gene mutations and variable expression of mast cell mediators. As a result, patients often present with chronic multisystem symptoms involving inflammatory, allergic, and dystrophic manifestations.
Because of this heterogeneity, identifying effective therapies can be challenging. Investigators proposed that targeting downstream inflammatory pathways may provide benefit regardless of the specific upstream molecular abnormalities present in individual patients.
The report describes what the authors identify as “the first case series showing utility of a variety of GLP-1RAs for managing refractory MCAS.” GLP-1 receptors are expressed on numerous cell types, including mast cells, providing a potential biologic rationale for therapeutic activity in the condition.
The case series included 47 patients with MCAS. The mean age was 39 years, with an age range of 15 to 71 years, and 89% of participants were female.
Clinical benefit was observed in the majority of patients. According to the authors, “89% demonstrated clinical benefit with GLP-1RAs for a broad range of problems associated with MCAS.” The report did not identify a single dominant symptom domain but instead described improvement across multiple manifestations of the syndrome.
GLP-1 receptor agonists are already approved for several chronic inflammatory conditions, including type 2 diabetes, obesity, and obstructive sleep apnea. The authors note growing interest in their broader anti-inflammatory effects across multiple disease states.
Reference
Afrin LB, Weinstock LB, Dempsey TT, Aschenbrenner K, Blitshteyn S, Schofield JR. Utility of glucagon-like-peptide-1-receptor agonists in mast cell activation syndrome. Am J Med Sci. 2025;370(4):377-382. doi:10.1016/j.amjms.2025.07.006
