Tseng Chin-Hsiao
Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 10051, Taiwan.
Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.
Pharmaceuticals (Basel). 2023 Feb 1;16(2):224. doi: 10.3390/ph16020224.
Whether metformin may reduce the risk of age-related macular degeneration (AMD) requires confirmation. This study compared the risk of AMD between ever users and never users of metformin matched on propensity score (PS) in Taiwanese patients with type 2 diabetes mellitus.
We enrolled study subjects from Taiwan's National Health Insurance. A total of 423,949 patients with new onset diabetes from 1999 to 2005 were identified. After excluding ineligible patients and enrolling only patients aged between 50 and 79 years, we created 13,303 pairs of ever users and never users of metformin matched on PS. The patients were followed from 1 January 2006 to 31 December 2011. We estimated hazard ratios by Cox regression.
AMD was newly diagnosed in 506 ever users and 639 never users. The respective incidence rates (per 100,000 person-years) were 778.72 and 1016.62. The hazard ratio (HR) and 95% confidence interval (CI) for ever versus never users was 0.756 (0.673-0.850). While ever users were categorized by tertiles of cumulative duration (<31.8, 31.8-63.9 and >63.9 months) and cumulative dose (<947.1, 947.1-2193.5 and >2193.5 g) of metformin, a dose-response pattern was observed. For the respective tertiles of cumulative duration, the HRs (95% CIs) were 1.131 (0.961-1.330), 0.821 (0.697-0.967) and 0.464 (0.384-0.561), while compared to never users. For the respective tertiles of cumulative dose, the HRs (95% CIs) were 1.131 (0.962-1.329), 0.739 (0.624-0.876) and 0.525 (0.438-0.629). A risk reduction among ever users was observed for all tertiles of defined daily dose but was most remarkable for the third tertile with a defined daily dose of >0.64. Subgroup analyses suggested that the benefit of metformin could be similarly observed among men and women and for age subgroups of 50-64 and 65-79 years. However, patients with diabetic retinopathy would not be significantly benefited and metformin did not seem to be preventive for exudative AMD.
In general, metformin significantly reduces the risk of AMD.
二甲双胍是否可降低年龄相关性黄斑变性（AMD）的风险尚需证实。本研究比较了台湾2型糖尿病患者中倾向评分（PS）匹配的二甲双胍既往使用者与未使用者发生AMD的风险。
我们从台湾国民健康保险中招募研究对象。共识别出1999年至2005年新诊断的423949例糖尿病患者。在排除不符合条件的患者并仅纳入年龄在50至79岁之间的患者后，我们创建了13303对PS匹配的二甲双胍既往使用者与未使用者。对患者从2006年1月1日至2011年12月31日进行随访。我们通过Cox回归估计风险比。
506例既往使用者和639例未使用者新诊断为AMD。各自的发病率（每10万人年）分别为778.72和1016.62。既往使用者与未使用者相比的风险比（HR）及95%置信区间（CI）为0.756（0.673 - 0.850）。当根据二甲双胍的累积疗程（<31.8、31.8 - 63.9和>63.9个月）和累积剂量（<947.1、947.1 - 2193.5和>2193.5 g）对既往使用者进行三分位数分类时，观察到剂量反应模式。对于累积疗程的各个三分位数，与未使用者相比，HR（95%CI）分别为1.131（0.961 - 1.330）、0.821（0.697 - 0.967）和0.464（0.384 - 0.561）。对于累积剂量的各个三分位数，HR（95%CI）分别为1.131（0.962 - 1.329）、0.739（0.624 - 0.876）和0.525（0.438 - 0.629）。在规定日剂量的所有三分位数中，既往使用者均观察到风险降低，但在规定日剂量>0.64的第三个三分位数中最为显著。亚组分析表明，在男性和女性以及50 - 64岁和65 - 79岁年龄亚组中均可类似地观察到二甲双胍的益处。然而，糖尿病视网膜病变患者未得到显著益处，且二甲双胍似乎对渗出性AMD无预防作用。
总体而言，二甲双胍可显著降低AMD的风险。
