Allan Kevin C, Joo Julia H, Kim Sonia, Shaia Jacqueline, Kaelber David C, Singh Rishi, Talcott Katherine E, Rachitskaya Aleksandra V
Case Western Reserve University School of Medicine, Cleveland, Ohio; Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio; Center for Ophthalmic Bioinformatics, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
Case Western Reserve University School of Medicine, Cleveland, Ohio; Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio; Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland Ohio.
Ophthalmology. 2025 Jul;132(7):748-757. doi: 10.1016/j.ophtha.2025.01.016. Epub 2025 Jan 23.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to exert neuroprotective and anti-inflammatory effects across multiple organ systems. This study investigated whether GLP-1RAs influence the risk for age-related ocular diseases.
Retrospective cohort study.
This study used an electronic health records platform of patients in the United States. Patients > 60 years with at least 5 years of ophthalmology follow-up and medication prescription documentation were included. There were 5 medication groups: GLP-1RA, metformin, insulin, statin, or aspirin users. Cohorts were propensity matched (1:1) on demographics and chronic disease risk factors.
Outcomes of cataract, ocular hypertension, primary open-angle glaucoma, nonexudative age-related macular degeneration (AMD), and exudative AMD were compared 5 years after initial medication prescription. We then examined earlier time points within the 5-year period. Significance was defined as P < 0.05 with a hazard ratio (HR) threshold of > 1.1 or < 0.9.
Of the 9669 patients taking GLP-1RAs, 84.4% had a diagnosis of diabetes with an average body mass index (BMI) of 36.2 kg/m. Propensity-matched cohorts demonstrated that GLP-1RAs were associated with a reduced hazard of nonexudative AMD compared with metformin (HR, 0.68; 95% CI, 0.56-0.84), insulin (HR, 0.72; 95% CI, 0.58-0.89), and statins (HR, 0.70; 95% CI, 0.57-0.87). These findings were validated compared with aspirin and in an independent older cohort of patients. This significant reduction appeared after 3 years compared with metformin (HR, 0.69; 95% CI, 0.52-0.91), insulin (HR, 0.66; 95% CI, 0.5-0.87), and statins (HR, 0.67; 95% CI, 0.51-0.88). Time course results were validated using independent cohorts of propensity-matched patients taking medications for 3 years. Notably, GLP-1RAs also significantly reduced the risk of exudative AMD (HR, 0.70; 95% CI, 0.58-0.84) and primary open-angle glaucoma (HR, 0.58; 95% CI, 0.45-0.76) compared with insulin after 3 years. Use of GLP-1RAs showed no persistent impact on the risk of cataract formation or ocular hypertension compared with other medications.
This study suggests that GLP-1RAs may reduce the risk of multiple age-related ocular diseases and the need for future prospective studies to validate these findings.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
胰高血糖素样肽-1受体激动剂（GLP-1RAs）已被证明可在多个器官系统中发挥神经保护和抗炎作用。本研究调查了GLP-1RAs是否会影响与年龄相关的眼部疾病的风险。
回顾性队列研究。
本研究使用了美国患者的电子健康记录平台。纳入年龄大于60岁、至少有5年眼科随访和药物处方记录的患者。共有5个药物组：GLP-1RA使用者、二甲双胍使用者、胰岛素使用者、他汀类药物使用者或阿司匹林使用者。各队列根据人口统计学和慢性病风险因素进行倾向评分匹配（1:1）。
在首次开具药物处方5年后，比较白内障、高眼压症、原发性开角型青光眼、非渗出性年龄相关性黄斑变性（AMD）和渗出性AMD的发生情况。然后我们检查了5年期间内更早的时间点。显著性定义为P<0.05，风险比（HR）阈值>1.1或<0.9。
在9669例服用GLP-1RAs的患者中，84.4%被诊断为糖尿病，平均体重指数（BMI）为36.2kg/m²。倾向评分匹配队列显示，与二甲双胍（HR，0.68；95%CI，0.56-0.84）、胰岛素（HR，0.72；95%CI，0.58-0.89）和他汀类药物（HR，0.70；95%CI，0.57-0.87）相比，GLP-1RAs与非渗出性AMD风险降低相关。与阿司匹林相比以及在一个独立的老年患者队列中，这些发现得到了验证。与二甲双胍（HR，0.69；95%CI，0.52-0.91）、胰岛素（HR，0.66；95%CI，0.5-0.87）和他汀类药物（HR，0.67；95%CI，0.51-0.88）相比，这种显著降低在3年后出现。使用倾向评分匹配的服用药物3年的独立患者队列验证了时间进程结果。值得注意的是，与胰岛素相比，3年后GLP-1RAs还显著降低了渗出性AMD（HR，0.70；95%CI，0.58-0.84）和原发性开角型青光眼（HR，0.58；95%CI，0.45-0.76）的风险。与其他药物相比，使用GLP-1RAs对白内障形成风险或高眼压症没有持续影响。
本研究表明，GLP-1RAs可能降低多种与年龄相关的眼部疾病的风险，未来需要进行前瞻性研究来验证这些发现。
在本文末尾的脚注和披露中可能会发现专有或商业披露信息。
