GLP-1RAs look good for idiopathic intracranial hypertension

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) appear promising in the management of idiopathic intracranial hypertension, with a retrospective study showing that the drugs reduce symptom burden as well as the need for medications and invasive procedures.

In a propensity-score matched cohort, GLP-1RA users were less likely to require any medication compared with nonusers (29.7 percent vs 56.4 percent; risk ratio [RR], 0.53, 95 percent confidence interval [CI], 0.46–0.61; p<0.001). Substantial reductions were observed in the use of tricyclic antidepressants (6.8 percent vs 12.3 percent; p=0.002), topiramate (11.2 percent vs 19.6 percent; p<0.001), furosemide (6.8 percent vs 14.4 percent; p<0.001), and acetazolamide (8.6 percent vs 24 percent; p<0.001). [JAMA Neurol 2025;82:887-894]

GLP-1RA use was associated with fewer symptoms and signs relative to nonuse, with a significantly lower prevalence of headache (12.3 percent vs 27.4 percent; p<0.001), visual disturbances/blindness (7 percent vs 11.7 percent; p=0.007), and papilledema (2.2 percent vs 11.5 percent; p<0.001).

Furthermore, procedural interventions were performed less frequently among GLP-1RA users vs nonusers (6.8 percent vs 15.7 percent; RR, 0.44, 95 percent CI, 0.30–0.63; p<0.001), including bariatric surgery (5.4 percent vs 10.1 percent; p=0.004) and cerebrospinal fluid (CSF) shunt procedures (1.8 percent vs 5.2 percent; p=0.002).

Mortality was significantly reduced with GLP-1RA use (2 percent vs 5 percent; RR, 0.36, 95 percent CI, 0.18–0.73; p=0.003), although BMI did not differ between users and nonusers (40.6 vs 39.5 kg/m²; p=0.10).

The analysis included 1,110 patients (average age 43 years, 86 percent female, 54.4 percent White, 66.9 percent had overweight/obesity) with idiopathic intracranial hypertension. Of these, 555 initiated GLP-1RA therapy within 6 months of diagnosis. The other half received conventional treatments, such as acetazolamide, topiramate, and dietary counselling, without GLP-1RA exposure. The median follow-up was 365 days for both groups. 

“This large, multicentre, retrospective propensity score–matched study provides valuable insights into the potential role of GLP-1 RAs in the management of idiopathic intracranial hypertension,” noted Dr Georgios Sioutas and colleagues from Virginia Commonwealth University Health System, Richmond, Virginia, US.

Existing evidence

The potential role of GLP-1RAs in the management of idiopathic intracranial hypertension has been explored in previous studies.

In a proof-of-concept trial involving 15 patients, treatment with exenatide led to a significant reduction in intracranial pressure as well as improvements in headache frequency and visual acuity at week 12. Another study that included 13 patients with idiopathic intracranial hypertension treated with semaglutide or liraglutide showed reductions in weight and headache days, although visual outcomes did not change. Generally, treatment with GLP1-RAs was associated with reduced acetazolamide doses. Some patients experienced mild gastrointestinal side effects, although these did not result in treatment discontinuation. [Brain 2023;146:1821-1830; Eye (Lond) 2024;38:1374-1379; J Headache Pain 2023;24:89]

“Together, these studies not only confirm the biological rationale for using GLP-1RAs in idiopathic intracranial hypertension but also highlight the need for larger, longer-term clinical studies to better define the efficacy, optimal dosing, and safety profiles in this patient population,” according to Sioutas and colleagues.

“Even though GLP-1RAs did not result in greater BMI reductions in our study, outcomes improved, suggesting a more complex mechanism of action. Other potential explanations for the results of our study include inconsistent follow-up for BMI, variable adherence to GLP-1RA therapy, and more bariatric surgeries in the control group,” they added.

Need for more studies

In an accompanying editorial, Dr Nancy Newman and colleagues from the Emory University School of Medicine, Atlanta, Georgia, US, echoed Sioutas and stressed the need for prospective studies to confirm GLP-1RA’s effectiveness, both as a monotherapy and in combination with other medications. [JAMA Neurol 2025;82:885-886]

“Prolonged weight loss is currently the only definitive treatment of idiopathic intracranial hypertension, and although the current cost of GLP-1 RAs may seem prohibitive compared to other medications used for idiopathic intracranial hypertension, surgical interventions (many of which fail over time and need to be repeated) are equally, or even more costly than GLP-1 RAs and generally have a greater potential for more serious complications,” Newman and colleagues wrote. [J Neurol Neurosurg Psychiatry 2018;89:1088-1100]

“It is time for [the] industry to recognize that the idiopathic intracranial hypertension patient population is unfortunately rapidly growing and a market worth testing with an appropriately designed clinical trial of GLP-1 RAs for idiopathic intracranial hypertension treatment,” they added. [Cephalalgia 2023;43:3331024231197118]