Abstract
INTRODUCTION: Idiopathic intracranial hypertension (IIH) is a neurological disorder characterised by elevated intracranial pressure (ICP), predominantly affecting obese women of reproductive age. While GLP-1 receptor agonists have shown promise in IIH management, the potential of dual GIP/GLP-1 receptor activation through tirzepatide remains unexplored. This study aimed to evaluate tirzepatide's efficacy as an adjunctive therapy in IIH management. METHODS: We conducted a retrospective cohort analysis using the TriNetX Global Health Research Network, analysing data through November 2024. Through propensity score matching, we compared 193 tirzepatide-exposed IIH patients with 193 controls receiving standard care. Primary outcomes included papilledema severity, visual function, headache frequency, and treatment resistance, monitored at multiple follow-up timepoints. RESULTS: Our analysis revealed significant improvements across all measured outcomes in the tirzepatide group. At 24 months, we observed a 68% reduction in papilledema risk (RR 0.320, 95% CI 0.189-0.542, p < 0.001), a 73.9% reduction in visual disturbance and blindness risk (RR 0.261, 95% CI 0.143-0.477, p < 0.001), and a 19.7% reduction in headache risk (RR 0.803, 95% CI 0.668-0.966, p = 0.019). The tirzepatide group demonstrated significant body-mass index reductions, reaching -1.147 kg/m(2) (95% CI [-1.415, -0.879], p < 0.001) at 24 months compared to controls. CONCLUSIONS: Our results demonstrate that tirzepatide, when used as an adjunctive therapy, provides significant therapeutic benefits in IIH management, particularly in improving papilledema and visual outcomes. Our findings suggest that dual GIP/GLP-1 receptor activation may offer advantages over traditional single-receptor therapies, potentially through enhanced metabolic regulation and direct effects on ICP dynamics.