Mohan Nitesh, Srivastava Sunil K, Schulgit Matthew J, Nowacki Amy S, Kaelber David C, Sharma Sumit
Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
Case Western Reserve University, Cleveland, Ohio.
JAMA Ophthalmol. 2025 Aug 28. doi: 10.1001/jamaophthalmol.2025.2822.
Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs), commonly used for glycemic control in diabetes, may possess anti-inflammatory properties. Understanding their potential protective role against uveitis could provide insights into novel therapeutic strategies.
To evaluate whether being prescribed a GLP-1RA is associated with a reduced risk of developing uveitis.
DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study using electronic health record (EHR) network data from 2006 to 2025. Propensity score matching was applied to control for demographics, smoking status, hypertension, body mass index, hemoglobin A1c, and diabetic retinopathy stage. Data from the US Collaborative Network of TriNetX, a large multicenter EHR platform, were used in this analysis. Included were patients with and without diabetes with prescriptions for GLP-1RAs, metformin, insulin, or sodium-glucose cotransporter 2 inhibitors (SGLT2is). The control groups consisted of patients without prescriptions for each medication.
Use of GLP-1RAs, metformin, insulin, or SGLT2is, identified through prescription records.
The primary outcome was the incidence of noninfectious uveitis, identified using International Classification of Diseases (ICD) encounter diagnosis codes. Risk ratios (RRs) with 95% CIs were calculated to assess the association between GLP-1RA use and uveitis risk. Analyses included risk of overall uveitis and subtypes such as chorioretinal inflammation, anterior uveitis, panuveitis, and retinal vasculitis.
A total of 516 052 patients were included in this study, 258 026 (mean [SD] age, 56.4 [13.7] years; 159 025 female [61.6%]) in the GLP-1RA group and 258 026 (mean [SD] age, 56.4 [14.0] years; 159 374 female [61.8%]) in the control group. The GLP-1RA cohort had a reduced risk of uveitis compared with controls (RR, 0.48; 95% CI, 0.46-0.51). This was consistent among those with type 2 diabetes (RR, 0.54; 95% CI, 0.51-0.58) and those without diabetes (RR, 0.52; 95% CI, 0.46-0.59). Compared with the cohorts taking metformin (RR, 0.58; 95% CI, 0.54-0.62) and insulin (RR, 0.57; 95% CI, 0.54-0.61), GLP-1RA prescriptions were associated with greater protection against uveitis. However, GLP-1RAs were associated with a slightly increased uveitis risk vs SGLT2is (RR, 1.17; 95% CI, 1.04-1.32). SGLT2i prescriptions were also associated with reduced uveitis risk compared with controls (RR, 0.52; 95% CI, 0.48-0.56).
This cohort study found that GLP-1RA prescriptions were associated with a lower risk of uveitis compared with controls. These findings suggest potential anti-inflammatory benefits beyond glycemic control, warranting further investigation into their role in ocular inflammatory diseases.
新出现的证据表明，常用于糖尿病血糖控制的胰高血糖素样肽-1受体激动剂（GLP-1RAs）可能具有抗炎特性。了解它们对葡萄膜炎的潜在保护作用可为新的治疗策略提供思路。
评估开具GLP-1RA处方是否与葡萄膜炎发病风险降低相关。
设计、设置和参与者：这是一项回顾性队列研究，使用了2006年至2025年的电子健康记录（EHR）网络数据。应用倾向评分匹配来控制人口统计学、吸烟状况、高血压、体重指数、糖化血红蛋白和糖尿病视网膜病变分期。本分析使用了来自大型多中心EHR平台美国TriNetX协作网络的数据。纳入了有或没有糖尿病且开具了GLP-1RA、二甲双胍、胰岛素或钠-葡萄糖协同转运蛋白2抑制剂（SGLT2is）处方的患者。对照组由未开具每种药物处方的患者组成。
通过处方记录确定使用GLP-1RA、二甲双胍、胰岛素或SGLT2is。
主要结局是非感染性葡萄膜炎的发病率，通过国际疾病分类（ICD）就诊诊断代码确定。计算95%置信区间的风险比（RRs）以评估GLP-1RA使用与葡萄膜炎风险之间的关联。分析包括总体葡萄膜炎风险以及脉络膜视网膜炎症、前葡萄膜炎、全葡萄膜炎和视网膜血管炎等亚型的风险。
本研究共纳入516052例患者，GLP-1RA组258026例（平均[标准差]年龄，56.4[13.7]岁；159025例女性[61.6%]），对照组258026例（平均[标准差]年龄，56.4[14.0]岁；159374例女性[61.8%]）。与对照组相比，GLP-1RA队列的葡萄膜炎风险降低（RR，0.48；95%置信区间，0.46 - 0.51）。在2型糖尿病患者（RR，0.54；95%置信区间，0.51 - 0.58）和非糖尿病患者（RR，0.52；95%置信区间，0.46 - 0.59）中也是如此。与服用二甲双胍（RR，0.58；95%置信区间，0.54 - 0.62）和胰岛素（RR，0.57；95%置信区间，0.54 - 0.61）的队列相比，GLP-1RA处方与预防葡萄膜炎的保护作用更强相关。然而，与SGLT2is相比，GLP-1RAs与葡萄膜炎风险略有增加相关（RR，1.17；95%置信区间，1.04 - 1.32）。与对照组相比，SGLT2i处方也与葡萄膜炎风险降低相关（RR，0.52；95%置信区间，0.48 - 0.56）。
这项队列研究发现，与对照组相比，GLP-1RA处方与较低的葡萄膜炎风险相关。这些发现表明，除血糖控制外，可能还有抗炎益处，值得进一步研究它们在眼部炎症性疾病中的作用。
