Li Yu-Ching, Huang Kuang-Hua, Yang Yih, Gau Shuo-Yan, Tsai Tung-Han, Lee Chien-Ying
Department of Health Services Administration, China Medical University, Taichung, Taiwan.
Department of Public Health, China Medical University, Taichung, Taiwan.
Clin Drug Investig. 2025 Mar;45(3):125-136. doi: 10.1007/s40261-025-01421-2. Epub 2025 Feb 12.
Recent research has raised concerns about the association between metformin treatment in patients with diabetes mellitus (DM) and an increased risk of diabetic retinopathy. We sought to investigate this relationship, specifically examining if metformin use affects diabetic retinopathy risk in a dose-dependent manner.
This study was a secondary data analysis based on a nationwide population database in Taiwan. Patients with new-onset DM, an age of 20 years or older, and a diagnosis of type 2 DM received at any time during 2002-2013 were included in the study. Patients diagnosed with new-onset type 2 DM between 2002 and 2013 were enrolled as the study population. We divided them into two groups: those treated with metformin and those treated with sulfonylureas. A Cox proportional hazards model was employed to estimate the risk of diabetic retinopathy after 5 years of follow-up, including cumulative defined daily dose and intensity of metformin treatment.
A total of 241,231 patients received treatment with metformin, while 152,617 patients were treated with sulfonylureas. Compared with patients treated with sulfonylureas, patients who received metformin treatment, at a cumulative defined daily dose < 30, had a lower risk of diabetic retinopathy (adjusted hazard ratio = 0.77; 95% confidence interval 0.60-0.98). However, those with varying defined daily doses, especially at a higher metformin treatment level (> 25 defined daily dose), had a 2.43 times higher risk of diabetic retinopathy (95% confidence interval 1.37-4.30) compared with patients treated with sulfonylureas.
Patients with DM treated with a lower cumulative dosage of metformin showed beneficial effects that were associated with a lower risk of diabetic retinopathy. In contrast, a higher intensity of metformin use had a greater risk of diabetic retinopathy.
近期研究引发了对糖尿病（DM）患者使用二甲双胍治疗与糖尿病视网膜病变风险增加之间关联的担忧。我们试图研究这种关系，特别考察二甲双胍的使用是否以剂量依赖方式影响糖尿病视网膜病变风险。
本研究是基于台湾全国人口数据库的二次数据分析。纳入2002年至2013年期间任何时间确诊为新发DM、年龄20岁及以上且诊断为2型DM的患者。2002年至2013年期间确诊为新发2型DM的患者被纳入研究人群。我们将他们分为两组：接受二甲双胍治疗的患者和接受磺脲类药物治疗的患者。采用Cox比例风险模型估计随访5年后糖尿病视网膜病变的风险，包括二甲双胍治疗的累积限定日剂量和强度。
共有241,231例患者接受二甲双胍治疗，而152,617例患者接受磺脲类药物治疗。与接受磺脲类药物治疗的患者相比，累积限定日剂量<30的接受二甲双胍治疗的患者发生糖尿病视网膜病变的风险较低（调整后风险比=0.77；95%置信区间0.60-0.98）。然而，与接受磺脲类药物治疗的患者相比，不同限定日剂量的患者，尤其是二甲双胍治疗水平较高（>25限定日剂量）的患者，发生糖尿病视网膜病变的风险高2.43倍（95%置信区间1.37-4.30）。
接受较低累积剂量二甲双胍治疗的DM患者显示出有益效果，这与较低的糖尿病视网膜病变风险相关。相比之下，较高强度使用二甲双胍会增加糖尿病视网膜病变的风险。
