OBJECTIVE: This study summarizes the evidence on the clinical effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in adults with idiopathic intracranial hypertension (IIH).
BACKGROUND: IIH is characterized by elevated intracranial pressure with normal neuroimaging and cerebrospinal fluid composition. Standard therapies (e.g., acetazolamide, topiramate) provide modest benefit and are often poorly tolerated. GLP-1 RAs, which induce weight loss and have been shown experimentally to reduce cerebrospinal-fluid secretion, are emerging as potential adjuncts, but clinical evidence has not been synthesized comprehensively.
METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and the World Health Organization-International Clinical Trials Registry Platform were searched from inception to July 2025. Human studies evaluating any GLP-1RA in IIH were eligible. Two reviewers independently screened records, extracted data, and appraised risk of bias (Risk Of Bias in Randomized Studies tool for randomized trials, Risk Of Bias In Nonrandomized Studies-of Interventions tool and Risk Of Bias In Nonrandomized Studies-of Exposures for observational cohorts, Joanna Briggs Institute for case reports). Heterogeneity and overlapping cohorts precluded meta-analysis; findings were synthesized narratively. The protocol was registered in International Prospective Register of Systematic Reviews (CRD420251058602).
RESULTS: Twelve reports met criteria: three randomized controlled trials, six retrospective cohorts, one case-control study, and two case reports. Across these studies, GLP-1RA treatment generally aligned with improvements in papilledema, headache burden, and body mass index, whereas visual outcomes and intracranial pressure data were more variable. The database cohorts suggested a consistent benefit, whereas findings in prospectively followed patients were mixed. Reported adverse effects were mostly mild gastrointestinal symptoms; some cohorts noted reduced reliance on acetazolamide and no cognitive decline. Evidence certainty was low because of observational designs, short follow-up, and nonstandardized outcome definitions.
CONCLUSION: Low-certainty evidence suggests GLP-1 RAs may reduce papilledema, headache burden, and body weight in IIH without apparent cognitive harm, but findings are inconsistent and driven largely by database analyses and small trials. Larger, well-powered randomized studies with uniform ophthalmic and headache endpoints, quality-of-life measures, and dose-response evaluation are needed to confirm efficacy and define long-term safety.
