Evidence for reduced migraine reporting with GLP-1 receptor agonists
Abstract
Abstract Migraine affects over one billion people worldwide, yet preventive options remain limited. Here, we provide convergent pharmacoepidemiological and mechanistic evidence that GLP-1 receptor agonist (GLP-1 RA) use is inversely associated with migraine. Analysing 16,998,128 deduplicated reports from the US FDA Adverse Event Reporting System (FAERS, 2004–2024), we found GLP-1 RA class use was inversely associated with migraine reporting (reporting odds ratio 0.759, 95% CI 0.720–0.801; E-value 1.96). Five of seven individual agents showed significant inverse associations, and all 18 prespecified subgroup analyses survived false discovery rate correction. Restrictive comparator analyses against SGLT2 inhibitors, DPP-4 inhibitors, and metformin confirmed a GLP-1 RA-specific signal. Independent analysis in the Japanese JADER database corroborated the inverse association for headache (ROR 0.226, 0.085–0.602). Network pharmacology and molecular docking identified favourable binding to migraine-relevant targets NOS3 and CALCRL. These findings provide a rationale for randomised trials evaluating GLP-1 RAs as migraine-preventive agents.
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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