Glucagon-like peptide-1 receptor agonists and the risk of surgical intervention in idiopathic intracranial hypertension: A propensity-matched cohort study

Mar 15, 2026Clinical neurology and neurosurgery

Glucagon-like peptide-1 receptor drugs and the risk of surgery in unexplained high brain pressure

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Abstract

GLP-1 receptor agonist exposure was associated with a 42% reduced incidence of ventriculoperitoneal shunt placement at 1 year.

GLP-1 receptor agonists may help in managing idiopathic intracranial hypertension (IIH) by contributing to weight loss and lowering intracranial pressure.
The incidence of ventriculoperitoneal shunt placement was significantly lower in patients using GLP-1 receptor agonists compared to those who were not, at both 1 year and 2 years.
A reduced incidence of venous sinus stenting was also observed in the GLP-1 receptor agonist group at both 1 year and 2 years.
No significant difference was found in the rates of optic nerve sheath fenestration between the two groups at either time point.

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OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as promising adjuncts for idiopathic intracranial hypertension (IIH) through weight loss and intracranial pressure modulation. Their impact on surgical intervention requirements remains unclear.

METHODS: We conducted a retrospective cohort study using the TriNetX Research Network. Adults with IIH (BMI ≥ 25 kg/m2) were included, excluding those with secondary causes of intracranial hypertension or prior surgical intervention. The exposed cohort (n = 7682) included patients prescribed a GLP-1 RA after IIH diagnosis. The control group (n = 54,775) consisted of unexposed patients. Propensity score matching (1:1) was performed for demographics, BMI, comorbidities, and medication use, yielding 6188 patients per cohort. The primary outcome was ventriculoperitoneal shunt (VPS) placement; secondary outcomes included venous sinus stenting (VSS) and optic nerve sheath fenestration (ONSF). Outcomes were assessed at 1- and 2-years using risk ratios and Cox survival analysis.

RESULTS: Following propensity score matching, GLP-1 RA exposure was associated with a significantly reduced incidence of VPS placement at both 1 year (RR 0.42; 95% CI 0.23-0.76; p = 0.003) and two years (RR 0.53; 95% CI 0.32-0.86; p = 0.009). VSS incidence was significantly lower in the GLP-1 RA cohort at both 1 year (RR 0.53; CI 0.32-0.88; p = 0.013) and 2 years (RR 0.56; CI 0.35-0.90; p = 0.015). ONSF rates did not differ significantly at either time point.

CONCLUSION: In this multi-institutional, propensity-matched cohort, GLP-1 RA use was associated with lower rates of VPS placement and VSS. These findings suggest a potential disease-modifying role for GLP-1 therapy in IIH and support prospective validation.

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Glucagon-like peptide-1 receptor agonists and the risk of surgical intervention in idiopathic intracranial hypertension: A propensity-matched cohort study

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