Efficacy of Tirzepatide Dual GIP/GLP-1 Receptor Agonist in Patients With Idiopathic Intracranial Hypertension. A Real-World Propensity Score-Matched Study

IF 2.7 Q3 ENDOCRINOLOGY & METABOLISM Endocrinology, Diabetes and Metabolism Pub Date : 2025-02-13 DOI:10.1002/edm2.70019

Ahmed Y. Azzam, Muhammed Amir Essibayi, Nathan Farkas, Mohammed A. Azab, Mahmoud M. Morsy, Osman Elamin, Adam Elswedy, Ahmed Saad Al Zomia, Hammam A. Alotaibi, Ahmed Alamoud, Oday Atallah, Hana J. Abukhadijah, Adam A. Dmytriw, Amanda Baker, Deepak Khatri, Neil Haranhalli, David J. Altschul

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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/m² (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.

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