Impact of GLP-1 receptor agonists on idiopathic intracranial hypertension clinical and neurosurgical outcomes: a propensity-matched multi-institutional cohort study

Sean O'Leary; Anthony Price; Liliana Camarillo-Rodriguez; Matias Costa; Patrick Karas; Christopher C Young; Visish M Srinivasan; Peter Kan

doi:10.3171/2025.1.JNS242357

Impact of GLP-1 receptor agonists on idiopathic intracranial hypertension clinical and neurosurgical outcomes: a propensity-matched multi-institutional cohort study

J Neurosurg. 2025 May 9:1-11. doi: 10.3171/2025.1.JNS242357. Online ahead of print.

Authors

Sean O'Leary¹, Anthony Price¹, Liliana Camarillo-Rodriguez¹, Matias Costa¹, Patrick Karas¹, Christopher C Young^{1

2}, Visish M Srinivasan³, Peter Kan¹

Affiliations

¹ 1Department of Neurosurgery, University of Texas Medical Branch, Galveston, Texas.
² 2Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas; and.
³ 3Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

PMID: 40344770
DOI: 10.3171/2025.1.JNS242357

Abstract

Objective: This study evaluated the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1-RAs) in idiopathic intracranial hypertension (IIH), focusing on their effects on clinical outcomes, management escalation, and mortality.

Methods: The authors conducted a cohort study using the TriNetX Research Network, comparing IIH patients treated with GLP-1-RAs to untreated patients, employing propensity score matching. Clinical outcomes, including headaches, visual and cognitive deficits, acetazolamide use, surgery, and mortality, were assessed at 6-month and 1-year follow-up (FU).

Results: At 6-month FU, 5750 patients in the GLP-1-RA cohort were matched to 5750 in the control group. At 1-year FU, 4968 patients in the GLP-1-RA cohort were matched to 4968 in the control group. The GLP-1-RA group demonstrated a significant reduction in BMI (p < 0.001) at 6 months, with a standardized mean difference of 1.083 kg/m2, which increased to 1.635 kg/m2 at 1 year. The control group showed a smaller reduction (p = 0.006), with a standardized mean difference of 0.695 kg/m2 at 6 months and 0.758 kg/m2 at 1 year. Furthermore, GLP-1-RA users had significantly lower odds of new-onset headache (OR 0.660, 95% CI 0.543-0.799, p < 0.001), visual deficits (OR 0.423, 95% CI 0.324-0.546, p < 0.001), cognitive deficits (OR 0.368, 95% CI 0.246-0.539, p < 0.001), and acetazolamide use (OR 0.295, 95% CI 0.249-0.348, p < 0.001) at 6 months. These trends persisted at 1 year for visual deficits (OR 0.606, 95% CI 0.489-0.747, p < 0.001), cognitive deficits (OR 0.590, 95% CI 0.432-0.801, p = 0.006), and acetazolamide use (OR 0.374, 95% CI 0.320-0.437, p < 0.001). Shunt placement for GLP-1-RA users also showed significantly lower risk at 1 year (OR 0.375, 95% CI 0.171-0.753, p = 0.047). Mortality rates were lower in the GLP-1-RA group at both 6 months (OR 0.060, 95% CI 0.031-0.106, p < 0.001) and 1 year (OR 0.115, 95% CI 0.070-0.179, p < 0.001). Kaplan-Meier survival curves confirmed these findings, additionally showing cumulative significance for headache reduction (p = 0.008).

Conclusions: GLP-1-RAs may provide clinical benefits for patients with IIH, improving outcomes and reducing the need for invasive interventions. Future randomized, prospective studies are warranted to confirm these findings and optimize treatment strategies.

Keywords: diabetes; glucagon-like peptide-1 receptor agonists; idiopathic intracranial hypertension; obesity; retrospective cohort study.