Glucagon-like Peptide-1 Receptor Agonists and Risk of Nonarteritic Anterior Ischemic Optic Neuropathy: Systematic Review and Meta-Analysis.

We aimed to synthesize the pooled evidence assessing the association between GLP-1RA use and NAION risk.

我们的目标是综合评估GLP-1RA使用与NAION风险之间关联的汇总证据。

Methods

Embase, Medline, and Cochrane CENTRAL databases were searched from inception to April 5, 2025.

从创刊至2025年4月5日，检索了Embase、Medline和Cochrane CENTRAL数据库。

Observational studies and randomized controlled trials comparing NAION risk in GLP-1RA users with non-GLP-1RA users were included.

纳入了比较GLP-1RA使用者与非GLP-1RA使用者中NAION风险的观察性研究和随机对照试验。

Title/abstract and full-text screening were conducted in duplicate by 2 independent reviewers.

标题/摘要和全文筛选由两位独立评审员分别进行。

Discrepancies were resolved through discussion or adjudication by a third reviewer.

分歧通过讨论或由第三位评审员裁决解决。

Risk of bias was assessed using the Risk of Bias In Nonrandomized Studies of Interventions (ROBINS-I) tool, and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation framework.

风险偏倚使用干预措施的非随机研究风险偏倚工具（ROBINS-I）进行评估，证据的确定性使用推荐、评估、发展和评估框架进行评估。

Pooled relative risks (RRs) were estimated using Bayesian random-effects models, incorporating half-normal, between-study, and weakly informative priors.

使用贝叶斯随机效应模型估计汇总相对风险（RRs），结合半正态、研究间和弱信息先验。

The RR with 95% credible interval (CrI) was computed to analyze the development of NAION associated with GLP-1RA exposure.

计算了与GLP-1RA暴露相关的非动脉炎性前部缺血性视神经病变（NAION）发展的相对风险（RR）及其95%可信区间（CrI），以进行分析。

Results

Five studies were included in the primary analysis, encompassing 1,593,554 patients (682,456 semaglutide users and 911,098 non-GLP-1RA users).

主要分析包括了五项研究，涵盖了1,593,554名患者（682,456名司美格鲁肽使用者和911,098名非GLP-1RA使用者）。

Semaglutide use was associated with a high probability of increased risk of NAION compared with non-GLP-1RA use (RR: 2.52, 95% CrI [1.56, 4.72], I2: 57.8%, P(RR > 1): 99.9%).

Semaglutide的使用与非GLP-1RA使用相比，与非动脉炎性前部缺血性视神经病变（NAION）风险增加的高概率相关（RR: 2.52, 95% CrI [1.56, 4.72], I2: 57.8%, P(RR > 1): 99.9%）

This association was particularly pronounced among patients with diabetes (RR: 2.41, 95% CrI [1.57, 4.10], I2: 47.2%, P(RR > 1): 99.9%).

这种关联在糖尿病患者中尤其明显（RR: 2.41, 95% CrI [1.57, 4.10], I2: 47.2%, P(RR > 1): 99.9%）

The overall incidenceof NAION across 5 studies and 7 comparisons, encompassing 1,460,760 patients (semaglutide: 1,108,542; dulaglutide: 326,282; and exenatide: 25,936) and 272 NAION events (semaglutide: 198; dulaglutide: 54; and exenatide: 20) was 85 cases per 100,000 GLP-1RA users (95% CrI [29, 263], I2: 98.8%, P(incidence>0.00001): 100%).

在5项研究和7个比较中，涵盖了1,460,760名患者（semaglutide：1,108,542；dulaglutide：326,282；exenatide：25,936）和272起NAION事件（semaglutide：198；dulaglutide：54；exenatide：20），GLP-1RA用户的NAION总发病率为每100,000人中85例（95% 置信区间[29, 263]，I2: 98.8%，P(发病率>0.00001): 100%）。

The incidenceof NAION across 1,108,542 semaglutide users was 118 cases per 100,000 (95% CrI [32, 451], I2: 98.8%, P(incidence>0.00001): 100%).

在1,108,542名semaglutide使用者中，NAION的发病率为每100,000人中118例（95% 置信区间[32, 451]，I2: 98.8%，P(发病率>0.00001): 100%）。

Leave-one-out sensitivity analyses consistently supported these findings.

逐个排除的敏感性分析一致支持这些发现。

Discussion

Low-to-moderate certainty evidence indicates that semaglutide significantly increases risk of NAION relative to non-GLP-1RAs, particularly among patients with diabetes.

低至中等质量的证据表明，与非GLP-1RAs相比，司美格鲁肽显著增加了糖尿病患者发生NAION的风险。

These findings warrant further investigation and should inform clinical risk-benefit discussions.

这些发现需要进一步调查，并应为临床风险-效益讨论提供信息。