J Neurosurg 143:1037–1047, 2025
This multicenter propensity-matched cohort study examines the association between glucagon-like peptide-1 receptor agonist (GLP-1-RA) therapy and clinical, neurosurgical, and mortality outcomes in adult patients with idiopathic intracranial hypertension (IIH) using the TriNetX electronic health record network. Outcomes at 6 months and 1 year include BMI change, new-onset headaches, visual and cognitive deficits, acetazolamide use, surgical interventions, and mortality.
Findings show greater weight loss and significantly lower odds of visual and cognitive deficits, acetazolamide use, shunt placement at one year, and markedly reduced all-cause mortality among GLP-1-RA users. The authors highlight biological plausibility, acknowledge limitations of retrospective administrative data, and call for randomized prospective trials to confirm causality and optimize treatment strategies.
• GLP-1 receptor agonists (GLP-1-RAs) are associated with significantly improved clinical outcomes in idiopathic intracranial hypertension (IIH), including reduced visual and cognitive deficits, headaches, acetazolamide use, need for shunt placement, and mortality compared to matched controls.
• Weight loss achieved with GLP-1-RAs is greater than with standard care: mean BMI reduction of 1.083 kg/m² at 6 months and 1.635 kg/m² at 1 year, versus 0.695 and 0.758 kg/m² in controls, respectively (p < 0.001).
• Odds of new-onset symptoms are significantly lower with GLP-1-RA treatment at 6 months for headache (OR 0.660), visual deficits (OR 0.423), cognitive deficits (OR 0.368), and acetazolamide use (OR 0.295); most effects persist at 1 year, including a significant reduction in shunt placement (OR 0.375).
• Mortality rates are substantially reduced in the GLP-1-RA group at both 6 months (OR 0.060) and 1 year (OR 0.115), with statistical significance confirmed by Kaplan-Meier survival analysis.
• Mechanisms of benefit may include both weight reduction and direct pharmacological effects, such as reduced cerebrospinal fluid secretion via GLP-1 receptors in the choroid plexus, and anti-inflammatory/neuroprotective actions in the brain.
• GLP-1-RA therapy allows for decreased reliance on acetazolamide, which is associated with more adverse effects, and offers a favorable safety profile—most commonly transient nausea.
• Study limitations include retrospective design, reliance on de-identified administrative data, inability to assess patient adherence, dosage, or causality, and residual confounding despite propensity score matching.
• Future directions call for larger, prospective randomized controlled trials to validate efficacy, clarify mechanisms (weight loss vs. direct CNS effects), and refine IIH treatment strategies.
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