Department of Ophthalmology and Visual Science, University of Chicago Medical Center, Chicago, Illinois.
Center for Health and the Social Sciences, The University of Chicago, Chicago, Illinois.
JAMA Ophthalmol. 2021 Mar 1;139(3):302-309. doi: 10.1001/jamaophthalmol.2020.6331.
Age-related macular degeneration (AMD), the leading cause of irreversible blindness in older adults, appears to have no effective preventive measures. The common antidiabetic drug metformin has been shown to have protective outcomes in multiple age-associated diseases and may have the potential to protect against the development of AMD.
To determine whether metformin use is associated with reduced odds of developing AMD.
DESIGN, SETTING, AND PARTICIPANTS: This case-control study of patients from a nationwide health insurance claims database included a population-based sample of patients. Those aged 55 years and older with newly diagnosed AMD from January 2008 to December 2017 were defined as cases and matched with control participants. Data analyses were completed from June 2019 to February 2020.
Dosage of metformin and exposure to other prescribed medications, as identified from outpatient drug claims.
Risk of developing AMD.
A total of 312 404 affected individuals were included (181 817 women [58.2%]). After matching, 312 376 control participants were included (172 459 women [55.2%]; age range, 55 to 107 years). The case group had a slightly higher percentage of participants with diabetes (81 262 participants [26.0%]) compared with the control group (79 497 participants [25.5%]). Metformin use was associated with reduced odds of developing AMD (odds ratio [OR], 0.94 [95% CI, 0.92-0.96]). This association was dose dependent, with low to moderate doses of metformin showing the greatest potential benefit (dosages over 2 years: 1-270 g, OR, 0.91 [95% CI, 0.88-0.94]; 271-600 g, OR, 0.90 [95% CI, 0.87-0.93]; 601-1080 g, OR, 0.95 [95% CI, 0.92-0.98]). Doses of more than 1080 g of metformin over 2 years did not have reduced odds of developing AMD. Both the reduction in odds ratio and the dose-dependent response were preserved in a cohort consisting only of patients with diabetes. Metformin use was associated with a decreased OR of AMD in patients with diabetes without coexisting diabetic retinopathy (OR, 0.93 [95% CI, 0.91-0.95]) but was a risk factor in patients with diabetic retinopathy (OR, 1.07 [95% CI, 1.01-1.15]).
In this study, metformin use was associated with reduced odds of developing AMD. This association was dose dependent, with the greatest benefit at low to moderate doses. When looking only at patients with diabetes, we saw a preservation of the dose-dependent decrease in the odds of patients developing AMD. Metformin does not appear to be protective in patients with diabetes and coexisting diabetic retinopathy. This study suggests that metformin may be useful as a preventive therapy for AMD and provides the basis for potential prospective clinical trials.
重要性：年龄相关性黄斑变性（AMD）是导致老年人不可逆性失明的主要原因，目前似乎没有有效的预防措施。常用的降糖药物二甲双胍已被证明对多种与年龄相关的疾病具有保护作用，可能具有预防 AMD 发展的潜力。
目的：确定二甲双胍的使用是否与降低 AMD 发病风险相关。
设计、地点和参与者：这项来自全国健康保险索赔数据库的患者病例对照研究纳入了一个基于人群的患者样本。2008 年 1 月至 2017 年 12 月新诊断为 AMD 的年龄在 55 岁及以上的患者被定义为病例，并与对照参与者相匹配。数据分析于 2019 年 6 月至 2020 年 2 月进行。
暴露：根据门诊药物索赔确定的二甲双胍剂量和其他处方药物的暴露情况。
主要结果和措施：AMD 发病风险。
结果：共纳入 312404 名受影响个体（181817 名女性[58.2%]）。匹配后，纳入 312376 名对照参与者（172459 名女性[55.2%]；年龄范围为 55 岁至 107 岁）。与对照组相比，病例组中患有糖尿病的参与者比例略高（81262 名参与者[26.0%]）。与对照组相比，二甲双胍的使用与降低 AMD 发病风险相关（比值比[OR]，0.94[95%CI，0.92-0.96]）。这种关联呈剂量依赖性，低至中等剂量的二甲双胍显示出最大的潜在益处（使用剂量超过 2 年：1-270 g，OR，0.91[95%CI，0.88-0.94]；271-600 g，OR，0.90[95%CI，0.87-0.93]；601-1080 g，OR，0.95[95%CI，0.92-0.98]）。超过 2 年使用剂量超过 1080 g 的二甲双胍并不能降低 AMD 的发病风险。无论是降低比值比还是剂量依赖性反应，在仅由患有糖尿病的患者组成的队列中均得到保留。在没有并发糖尿病性视网膜病变的糖尿病患者中，二甲双胍的使用与 AMD 发病风险降低相关（OR，0.93[95%CI，0.91-0.95]），但在患有糖尿病性视网膜病变的患者中是一个风险因素（OR，1.07[95%CI，1.01-1.15]）。
结论和相关性：在这项研究中，二甲双胍的使用与降低 AMD 发病风险相关。这种关联呈剂量依赖性，低至中等剂量的二甲双胍效果最佳。当仅观察患有糖尿病的患者时，我们看到了患者发病风险随剂量降低的相关性得以保留。二甲双胍似乎对患有糖尿病和并发糖尿病性视网膜病变的患者没有保护作用。本研究表明，二甲双胍可能对 AMD 有预防作用，并为潜在的前瞻性临床试验提供了依据。
