Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, MI, USA.
Center for Preventive Ophthalmology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Eur J Ophthalmol. 2022 Jan;32(1):417-423. doi: 10.1177/1120672121997288. Epub 2021 Feb 19.
To assess whether metformin is associated with dry age-related macular degeneration (dAMD) development.
In this retrospective cohort study, patients enrolled in a nationwide U.S. medical insurance claims database from 2002 to 2016 were included if they had diabetes mellitus, were ⩾55 years old, and were enrolled for ⩾2 years without a prior AMD diagnosis. The primary exposure was metformin use analyzed as either active or prior use or cumulative metformin dosage over the study period. A time updating Cox proportional hazard regression was used to estimate the hazard ratio of dAMD incidence with metformin exposure.
Among 1,007,226 diabetic enrollees, 53.3% were female and 66.4% were white with a mean hemoglobin A1c of 6.8%. Of eligible enrollees, 166,115 (16.5%) were taking metformin at the index date. Over the study period, 29,818 (3.0%) participants developed dAMD. In the active versus prior use of metformin model, active use conferred an increased hazard of developing dAMD (HR, 1.08; 95% CI, 1.04-1.12) while prior use had a decreased hazard (HR, 0.95; 95% CI 0.92-0.98). The cumulative metformin dosage model showed a significant trend toward increased hazard of dAMD incidence with increasing cumulative dosage ( < 0.001), with the lowest dosage quartile having decreased hazard of dAMD incidence (HR, 0.95; 95% CI, 0.91-0.99) and the highest having increased hazard (HR, 1.07; 95% CI, 1.01-1.13).
Small, conflicting associations between metformin exposure and development of dAMD were observed depending on cumulative dosage and whether drug use was active, suggesting metformin did not substantially affect the development of dAMD.
评估二甲双胍是否与干性年龄相关性黄斑变性（dAMD）的发展相关。
本回顾性队列研究纳入了 2002 年至 2016 年期间参加美国全国性医疗保险索赔数据库的患者，如果他们患有糖尿病，年龄 ⩾55 岁，并且在没有先前 AMD 诊断的情况下入组 ⩾2 年。主要暴露因素为二甲双胍的使用情况，分析为活跃使用或先前使用或研究期间的累积二甲双胍剂量。采用时间更新的 Cox 比例风险回归来估计二甲双胍暴露与 dAMD 发病率的风险比。
在 1007226 名糖尿病患者中，53.3%为女性，66.4%为白人，平均糖化血红蛋白为 6.8%。在合格的入组患者中，有 166115 人（16.5%）在索引日期正在服用二甲双胍。在研究期间，有 29818 名（3.0%）参与者发生了 dAMD。在二甲双胍的活跃使用与先前使用模型中，活跃使用增加了发生 dAMD 的风险（HR，1.08；95%CI，1.04-1.12），而先前使用降低了风险（HR，0.95；95%CI，0.92-0.98）。累积二甲双胍剂量模型显示出 dAMD 发病率随累积剂量增加而显著增加的趋势（ < 0.001），最低剂量四分位数降低了 dAMD 发病率的风险（HR，0.95；95%CI，0.91-0.99），最高剂量四分位数增加了风险（HR，1.07；95%CI，1.01-1.13）。
根据累积剂量以及药物使用是否活跃，观察到二甲双胍暴露与 dAMD 发展之间存在微小、相互矛盾的关联，表明二甲双胍并未显著影响 dAMD 的发展。
