Introduction: Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial
pressure without a clear cause and is associated with increased risk of headaches,
visual disturbances, spontaneous cerebrospinal fluid leak (CSF), encephalocele, and
papilledema. While obesity and metabolic dysfunction are key risk factors, the pathophysiology
of IIH remains poorly understood. Anti-obesity medications, including glucagon-like
peptide-1 receptor agonists (GLP-1) and GLP-1/gastric inhibitory polypeptide (GIP)
combinations like tirzepatide, are being investigated for their potential in IIH management.
These agents may exert beneficial effects by modulating cerebrospinal fluid dynamics,
reducing neuroinflammation, and promoting weight reduction. This study evaluates their
efficacy and safety in modifying disease progression and improving outcomes for IIH
patients.
Methods: A comparative outcomes analysis was conducted using the TriNetX platform, which leverages
electronic medical records from 94 healthcare organizations. Two cohorts were defined:
Cohort 1 (n = 2,617,891) included patients not on anti-obesity medications post–June 2021, and
Cohort 2 (n = 280,775) comprised patients with overweight or obesity on anti-obesity medications
(GLP-1 or GLP-1/GIP combinations) from June 1, 2021, onward. Propensity score matching
was applied to balance the cohorts for demographic and clinical characteristics, resulting
in matched groups of 280,669 patients each. Key outcomes analyzed included the incidence
of IIH, CSF leaks, CSF leak repair, papilledema, vision changes, and blindness. Risk
is reported as risk ratios.
Results: The matched cohorts were comparable in age (mean age: 51.4 vs. 51.3 years), gender
distribution (64.1% female in Cohort 1 vs. 64.0% in Cohort 2), and type 2 diabetes
prevalence (44.1% in Cohort 1 vs. 44.0% in Cohort 2). The risk of developing IIH was
slightly higher in Cohort 1 (0.15%) compared to Cohort 2 (0.13%), but the risk ratio
(1.10, 95% CI: 0.95–1.26) was not significant (p = 0.198). Papilledema risk was similar (0.1% in both cohorts; p = 0.890). However, significant differences were found for other outcomes: the risk
of CSF leaks was higher in Cohort 1 (0.08%) compared to Cohort 2 (0.05%), with a risk
ratio of 1.73 (95% CI: 1.39–2.16, p < 0.001). Vision changes and blindness were also more frequent in Cohort 1, with
risk ratios of 1.25 (95% CI: 1.19–1.32, p < 0.001) and 1.43 (95% CI: 1.33–1.54, p < 0.001), respectively. Notably, the need for surgical repair was significantly higher
in Cohort 1 (0.03%) compared to Cohort 2 (0.01%), with a risk ratio of 3.88 (95% CI:
2.47–6.07).
Conclusion: The analysis suggests that anti-obesity medications may have a protective effect
on certain outcomes associated with IIH, such as CSF leaks, vision changes, and blindness,
although the direct impact on IIH risk was not significant. These findings support
the potential role of anti-obesity medications in reducing complications related to
IIH and underscore the need for further clinical studies to explore their efficacy
and safety in this context. The propensity-matched analysis provides a strong basis
for future research on therapeutic strategies for IIH, particularly in populations
at high risk due to obesity and metabolic dysfunction.
