Luciano Falcão, Leonardo B O Brenner, Pedro Lucas Machado Magalhães, Abhishek Goyal, Mariana Leticia de Bastos Maximiano, Kenzo Ogasawara Donato, Rafael Andrade Sampaio Silva, Joao Victor Pereira Gonzalez, da Silva, Anderson Silva Corin, Katherine Zarroli
GLP-1 RAs appear associated with improvements in clinical outcomes in IIH, including reductions in papilledema, headache, and visual symptoms. The current evidence base is dominated by observational studies with moderate to serious risk of confounding, resulting in low-certainty, hypothesis-generating evidence. These findings should be interpreted cautiously and primarily serve to inform the design of future well powered randomized controlled trials.
OBJECTIVES/BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed for type 2 diabetes and obesity, have emerged as promising candidates for idiopathic intracranial hypertension (IIH) due to their metabolic and neurophysiological effects. This systematic review and meta-analysis aims to summarize, synthesize, and quantitatively pool the available evidence on the use of GLP-1 RAs in patients with IIH, focusing on clinical outcomes.
METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched through December 2025 for randomized trials and cohort studies assessing GLP-1 RAs in patients with IIH. Risk of bias was assessed by Risk of Bias in Nonrandomized Studies of Interventions and Cochrane Risk of Bias 2.0. Primary outcomes included papilledema, headache burden, refractory IIH, and visual disturbances.
RESULTS: Eight studies comprising 13,243 patients met inclusion criteria. GLP-1 RAs significantly reduced papilledema risk at 3 months (risk ratio [RR], 0.430; 95% confidence interval [CI], 0.281-0.659; I-squared statistic [I2] = 62.5%) and maintained the benefit through 24 months (RR, 0.469; 95% CI, 0.382-0.576; I2 = 18.0%). Headache frequency was also consistently lower at 3 months (RR, 0.690; 95% CI, 0.557-0.853; I2 = 71.0%) and at 24 months (RR, 0.796; 95% CI, 0.691-0.916; I2 = 68.9%), with similar improvements in visual disturbances at 3 months (RR, 0.408; 95% CI, 0.304-0.547; I2 = 36.0%) and 24 months (RR, 0.433; 95% CI, 0.236-0.796; I2 = 79.0%), and refractory IIH at 3 months (RR, 0.696; 95% CI, 0.574-0.843; I2 = 60.0%) and 24 months (RR, 0.808; 95% CI, 0.715-0.908; I2 = 52.0%) compared to control group.
CONCLUSION: GLP-1 RAs appear associated with improvements in clinical outcomes in IIH, including reductions in papilledema, headache, and visual symptoms. The current evidence base is dominated by observational studies with moderate to serious risk of confounding, resulting in low-certainty, hypothesis-generating evidence. These findings should be interpreted cautiously and primarily serve to inform the design of future well powered randomized controlled trials.