Utility of glucagon-like-peptide-1-receptor agonists in mast cell activation syndrome.

This case-series reports on 47 patients with refractory mast cell activation syndrome treated with glucagon-like peptide-1 receptor agonists (GLP-1RAs). Because GLP-1 receptors exist on mast cells and other immune/metabolic cells, the authors hypothesized these drugs—already used for type 2 diabetes, obesity, and obstructive sleep apnea—might downregulate inflammatory pathways relevant to MCAS. In this diverse cohort (mean age 39, 89% female), 89% experienced clinical benefit across a broad range of MCAS-related symptoms. The paper underscores MCAS’s molecular and clinical heterogeneity and proposes targeting downstream effectors like GLP-1 signaling as a practical strategy when upstream drivers vary. The authors conclude GLP-1RAs may offer substantial benefit for MCAS and call for randomized controlled trials to define efficacy, safety, and optimal dosing in this population.