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Meta-Analysis
. 2025 Sep;32(9):e70358.
doi: 10.1111/ene.70358.

Efficacy and Safety of GLP-1 and Dual GIP/GLP-1 Receptor Agonists in Idiopathic Intracranial Hypertension: A Systematic Review and Meta-Analysis

Maria-Ioanna Stefanou  1   2 , Irini Chatziralli  3 , Vaia Lambadiari  4 , Annerose Mengel  2   5 , Aikaterini Foska  1 , Maria Chondrogianni  1 , Eleni Bakola  1 , Panagiota-Eleni Tsalouchidou  1 , Dimos D Mitsikostas  6 , Gerasimos Siasos  7 , Ulf Ziemann  2   5 , Georgios Tsivgoulis  1
Affiliations
Meta-Analysis

Efficacy and Safety of GLP-1 and Dual GIP/GLP-1 Receptor Agonists in Idiopathic Intracranial Hypertension: A Systematic Review and Meta-Analysis

Maria-Ioanna Stefanou et al. Eur J Neurol. 2025 Sep.

Abstract

Background: Repurposing glucagon-like peptide-1 (GLP-1) and GIP/GLP-1 receptor agonists (RAs) for idiopathic intracranial hypertension (IIH) represents an attractive alternative to current treatments, supported by evidence of potent metabolic effects and reductions in cerebrospinal fluid secretion and intracranial pressure in vivo.

Methods: We evaluated the safety and efficacy of GLP-1 RAs and GIP/GLP-1 RAs in IIH. MEDLINE and Scopus databases were searched for randomized-controlled trials (RCT), non-randomized clinical trials, or registries in adults with IIH.

Results: Two clinical trials (one RCT and one non-randomized case-control) and two registries, comprising 1550 IIH patients (768 receiving GLP-1 or GIP/GLP-1 RAs) were included. Compared with standard-of-care, GLP-1 or GIP/GLP-1 RAs were associated with a significantly lower risk of papilledema (RR: 0.25; 95% CI: 0.15-0.43; p < 0.01) and visual disturbances or blindness (RR: 0.41; 95% CI: 0.18-0.92; p = 0.03), and a near-significant trend toward reduced headache risk (RR: 0.61; 95% CI: 0.34-1.07; p = 0.08). Additionally, GLP-1 RAs significantly reduced monthly headache days at 3 months (MD = -3.64; 95% CI: -6.26 to -1.03; p < 0.01) and at the end of follow-up (MD = -4.82; 95% CI: -8.80 to -0.85; p = 0.02). No association was detected between GLP-1 RAs and body mass index. No serious adverse events or treatment discontinuations were reported; mild gastrointestinal adverse events and nausea occurred in 88% (95% CI: 0.46-1.00) of GLP-1 RA-treated patients.

Conclusions: GLP-1 and dual GIP/GLP-1 RAs are associated with a significantly lower risk of papilledema and visual disturbances or blindness and a lower headache risk compared with standard-of-care. Additionally, GLP-1 RAs significantly reduce the monthly headache burden. Well-designed RCTs are needed to robustly evaluate the effects of GLP-1 and GIP/GLP-1 RAs in IIH, which likely extend beyond their weight-loss-inducing properties.

Trial registration: PROSPERO registration ID: CRD42025650082.

Keywords: GIP/GLP‐1; GLP‐1; exenatide; headache; intracranial hypertension; tirzepatide.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Forest plot comparing the risk of (a) papilledema (b) visual disturbances or blindness, and (c) headache in IIH patients treated with GLP‐1 or GIP/GLP‐1 RAs versus controls.
FIGURE 2
FIGURE 2
Forest plot comparing the change in monthly headache days in GLP‐1 RA treated IIH patients versus controls (a) at 3 months and (b) at the end of follow‐up.
FIGURE 3
FIGURE 3
Forest plot comparing the change in visual acuity in GLP‐1 RA treated IIH patients versus controls (a) at 3 months and (b) at the end of follow‐up.
See this image and copyright information in PMC

References

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