BACKGROUND: Idiopathic intracranial hypertension (IIH) is a debilitating neurologic condition marked by elevated intracranial pressure (ICP), typically affecting obese women of reproductive age. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), widely used for obesity and diabetes, have recently emerged as potential therapeutic agents for IIH.
OBJECTIVE: To systematically evaluate the efficacy and safety of GLP-1 RAs in IIH, based on clinical studies reporting outcomes related to ICP, headache, vision, cognition, weight loss, and safety.
METHODS: A systematic search was conducted across MEDLINE, Scopus, and Web of Science up to June 15, 2025, using PRISMA 2020 guidelines. Studies involving adult IIH patients treated with GLP-1 RAs and reporting relevant clinical outcomes were included. Data extraction and bias assessment were performed independently by multiple reviewers.
RESULTS: Nine clinical studies (one RCT, eight observational studies) with IIH patients receiving GLP-1 RAs were included. GLP-1 RA use was consistently associated with improvements in headache frequency, weight reduction, and reduced need for acetazolamide or surgical interventions. In a small RCT, exenatide significantly lowered ICP within hours of administration. Several studies reported papilledema resolution and a lower risk of visual deterioration. Cognitive function either improved or remained stable. Adverse effects were mostly mild gastrointestinal symptoms; no serious safety concerns emerged. Interpretation is limited by the predominance of potentially overlapped retrospective data and minimal randomized evidence.
CONCLUSION: GLP-1 RAs show promise as a disease-modifying therapy for IIH, with potential benefits beyond weight loss. The consistency of findings across multiple studies and data sources provides justification of a shift in research focus to conduct well-powered phase 3 randomized controlled trials to validate these preliminary findings and define optimal treatment strategies.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10194-025-02148-3.
GLP-1 Therapies