GLP-1 Receptor Agonists in Idiopathic Intracranial Hypertension

Georgios S. Sioutas, MD1; William Mualem, MD1; John Reavey-Cantwell, MD, MBA, MS1; et al

2025년07월14일

JAMA Neurol. Published online: July 14, 2025

DOI:10.1001/jamaneurol.2025.2020

Abstract

Importance   Current treatment options for idiopathic intracranial hypertension (IIH) are limited by efficacy, safety, and sustainability concerns. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), known for promoting weight loss and metabolic regulation, may offer a novel therapeutic approach.

Objective   To assess whether GLP-1 RA therapy is associated with improved clinical outcomes in patients with IIH compared with conventional therapies.

Design, Setting, and Participants   This retrospective cohort study was conducted using data from the TriNetX US Collaborative Network between 2005 and 2024, with a follow-up duration of 1 year. Electronic health records from 67 health care organizations across the United States were examined. Participants were patients 18 years and older who had IIH.

Exposure   Initiation of GLP-1 RA therapy within 6 months of IIH diagnosis. The control group included patients managed with conventional treatments, such as acetazolamide, topiramate, and dietary counseling, without GLP-1 RA exposure.

Main Outcome and Measures   Outcomes included use of non–GLP-1 RA medication, symptoms and signs, procedures, and mortality over 1 year. Outcomes were expressed as risk ratios (RRs) with 95% CI.

Results   A total of 44 373 patients with IIH were identified. Before propensity score matching, the cohort included 603 GLP-1 RA users and 43 770 nonusers. The GLP-1 RA group was older (mean [SD] age, 43.2 [13.0] vs 35.5 [14.3] years; P < .001) with fewer male patients (n = 60 [10.0%] vs n = 5879 [13.5%]; P = .01) and a similar number of female patients (n = 522 [86.6%] vs n = 36 796 [84.3%]; P = .13). After matching, 555 GLP-1 RAs users were compared with 555 nonusers. GLP-1 RA use was associated with lower medication use (RR, 0.53; 95% CI, 0.46-0.61; P < .001) and reduced headaches (RR, 0.45; 95% CI, 0.35-0.58; P < .001), visual disturbances or blindness (RR, 0.60; 95% CI, 0.41-0.88; P = .007), and papilledema (RR, 0.19; 95% CI, 0.10-0.34; P < .001). Procedures (RR, 0.44; 95% CI, 0.30-0.63; P < .001) and mortality (RR, 0.36; 95% CI, 0.18-0.73; P = .003) were lower in the GLP-1 RA group, but mean (SD) body mass index (BMI) did not differ at follow-up (40.6 [9.2] vs 39.5 [8.7]; P = .10). Sensitivity analysis stratified by BMI (≥40 vs <40) showed similar associations. Bariatric surgery was associated with greater weight loss, but GLP-1 RA therapy was associated with better outcomes.

Conclusions and Relevance   GLP-1 RA therapy in IIH is associated with significant reductions in medication use, symptoms/signs, and procedural interventions, suggesting its potential as a management strategy. Further prospective studies are warranted to confirm these findings.

Figure 2.  Risk Ratios (RRs) With 95% CI for Outcomes at 1 Year

Key Points

Question   Does glucagon-like peptide 1 receptor agonist (GLP-1 RA) therapy improve the management of idiopathic intracranial hypertension (IIH) compared with conventional therapies?

Findings   In this cohort study using data from the TriNetX US Collaborative Network and involving 1110 propensity score–matched patients with IIH, GLP-1 RA therapy was associated with significantly lower medication use, fewer symptoms and signs, and reduced need for procedural interventions over a 1-year follow-up period.

Meaning   GLP-1 RA therapy may offer an alternative management strategy for IIH, warranting further prospective evaluation.

요약

·         중요성 : 현재 특발성 두개내압상승증(IIH)의 치료 옵션은 효과, 안전성 및 지속 가능성 측면에서 한계가 있다. 체중 감소 및 대사 조절에 효과가 있는 것으로 알려진 GLP-1 RA는 새로운 치료 접근법이 될 수 있다.

·         목적 : GLP-1 RA 치료가 기존 치료와 비교하여 IIH 환자의 임상 결과 개선과 연관이 있는지 평가한다.

·         설계, 환경 및 참가자 : 후향적 코호트 연구로 2005년부터 2024년까지 미국 전역 67개 의료기관의 전자의무기록(EHR)을 기반으로 TriNetX US Collaborative Network 데이터를 활용하였다. 대상자는 18세 이상 IIH 진단을 받은 환자로, 추적기간은 1년이었다.

·         중재 :  IIH 진단 후 6개월 이내에 GLP-1 RA 치료를 시작한 환자. 대조군은 GLP-1 RA를 사용하지 않고 아세타졸아미드, 토피라메이트, 식이 상담 등 기존 치료만 받은 환자였다.

·         주요 결과 및 측정 :  1년간 비(GLP-1 RA) 약물 사용, 증상 및 징후, 시술, 사망률을 평가했다. 결과는 위험비(RR)와 95% 신뢰구간(CI)로 표현하였다.

·          결과 : 총 44,373명의 IIH 환자가 확인되었으며, 성향점수 매칭 전에는 GLP-1 RA 사용자가 603명, 비사용자가 43,770명이었다. GLP-1 RA군은 평균 연령이 더 높았고(43.2세 vs 35.5세, P<.001), 남성 비율이 더 낮았으며(10.0% vs 13.5%, P=.01), 여성 비율은 비슷했다(86.6% vs 84.3%, P=.13).

성향점수 매칭 후 GLP-1 RA 사용자 555명과 비사용자 555명을 비교하였다. GLP-1 RA 사용은

- 약물 사용 감소(RR 0.53; 95% CI 0.46–0.61; P<.001),

- 두통 감소(RR 0.45; 95% CI 0.35–0.58; P<.001),

- 시야장애·실명 감소(RR 0.60; 95% CI 0.41–0.88; P=.007),

- 유두부종 감소(RR 0.19; 95% CI 0.10–0.34; P<.001),

- 시술 필요성 감소(RR 0.44; 95% CI 0.30–0.63; P<.001),

- 사망률 감소(RR 0.36; 95% CI 0.18–0.73; P=.003)와 연관되었다.

그러나 추적 시 평균 BMI는 유의한 차이가 없었다(40.6 vs 39.5; P=.10). BMI ≥40 vs <40으로 층화한 민감도 분석에서도 유사한 결과가 나왔다. 비만수술은 더 큰 체중 감소와 연관되었으나, GLP-1 RA 치료가 더 나은 임상결과와 연관되었다.

·         결론 및 의의 : GLP-1 RA 치료는 IIH 환자에서 약물 사용, 증상·징후 및 시술 필요성을 유의하게 줄여, 관리 전략으로서의 가능성을 시사한다. 이를 확인하기 위한 추가 전향적 연구가 필요하다.