目的：探讨2型糖尿病(type 2 diabetes mellitus，T2DM)患者二甲双胍治疗与糖尿病性视网膜病变(diabetic retinopathy，DR)的相关性。方法：回顾2015年9月至2020年8月在中日友好医院眼科就诊的1 891例T2DM患者的临床资料，对病程≥10年的324例T2DM患者的一般资料、内科疾病史、糖尿病治疗史、眼科检查和实验室血生化指标进行回顾性病例研究。根据是否接受二甲双胍治疗分为二甲双胍治疗组与非二甲双胍治疗组，根据眼底检查结果同时结合DR临床诊断标准，将DR分为无明显DR、非增生性DR及增生性DR。采用logistic多因素回归分析判断年龄、性别、糖尿病发病年龄、糖尿病病程、高血压病程、高血脂病程、吸烟年数、体重指数、胰岛素治疗及空腹血糖、糖化血红蛋白、总胆固醇、三酰甘油、尿酸和血肌酐水平对结局变量的影响。结果：在DR的发病风险方面，二甲双胍治疗组与非二甲双胍治疗组的差异无统计学意义(P>0.05)。对T2DM患者DR发生及不同分期的相关变量行单因素及多因素分析，结果显示吸烟年数、空腹血糖及肌酐均与DR发病呈正相关(均P<0.05)，而年龄与DR发病呈负相关(P<0.01)，糖尿病发病年龄与DR发生呈显著负相关(OR=0.95，95%CI：0.92~0.98，P=0.0003)。在二甲双胍治疗的T2DM患者中，二甲双胍的疗程(OR=1.02，95%CI：0.96~1.08，P>0.05)及平均剂量(OR=1.50，95%CI：0.79~2.84，P>0.05)与DR的发生与进展均无显著相关性；女性DR发生与进展的风险较男性低(P<0.05)；合并胰岛素治疗与DR发生呈明显正相关(OR=3.11，95%CI：1.59~6.07，P<0.01)；吸烟年数长、糖化血红蛋白及尿酸水平高于正常范围均与DR的发生与进展呈正相关(P<0.05)。在口服二甲双胍患者中，未使用胰岛素治疗组和联合使用胰岛素组的DR发病风险有显著差异(P<0.01)；而未口服二甲双胍患者中，胰岛素治疗与DR发生呈正相关(OR=12.43，95%CI：3.75~41.19，P<0.0001)。结论：病程10年以上T2DM患者中，二甲双胍治疗与DR发生与进展均无显著相关性。

Objective: To investigate the correlation between metformin therapy and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods: The clinical data of 1 891 patients with type 2 diabetes mellitus attending the ophthalmology department of China-Japan Friendship Hospital from September 2015 to August 2020 were reviewed. A retrospective study was performed on 324 cases of these T2DM patients with disease duration ≥10 years. Medical records of all patients including general information, history of medical disease, diabetes treatment, ophthalmologic examination and blood biochemical indices were collected. According to whether metformin treatment was received or not, the patients were divided into a metformin-treated and a non-metformin-treated groups. DR is classified into non-obvious DR, non-proliferative DR and proliferative DR according to the fundus examination and the clinical diagnostic criteria of DR. Logistic multiple regression analysis was used to determine the effects of age, sex, age of DM onset, duration of DM, duration of hypertension,

duration of hyperlipidemia, years of smoking, body mass index, insulin treatment and fasting glucose, glycated hemoglobin, total cholesterol, triglycerides, uric acid and blood creatinine levels on DR. Results: There was no statistically significant difference in the risk of developing DR between the metformin-treated and non-metformin-treated groups (P>0.05). Univariate and multifactorial analyses of variables related to the occurrence and different stages of DR in patients with T2DM showed that years of smoking, fasting glucose and creatinine were positively associated with DR (P<0.05), while age was negatively associated with DR (P<0.01), and age of DM onset was significantly negatively associated with DR (OR=0.95, 95%CI: 0.92 to 0.98, P=0.0003). In T2DM patients treated with metformin, neither the duration of metformin (OR=1.02, 95%CI: 0.96 to 1.08, P>0.05) nor the mean dose(OR=1.50, 95%CI: 0.79 to 2.84, P>0.05) was significantly associated with developing DR. The risk of developing DR was lower in women than in men (P<0.05); combined insulin therapy was significantly positively correlated with the risk of DR (OR=3.11, 95%CI: 1.59 to 6.07, P<0.01); long-term smoking, glycosylated hemoglobin and uric acid levels higher than normal were positively associated with DR (P<0.05). In metformin users, there was a significant difference in the risk of developing DR between the no-insulin treatment group and the combined insulin group (P<0.01); and among patients not using metformin, insulin therapy was positively associated with the occurrence of DR (OR=12.43, 95%CI: 3.75 to 41.19, P<0.0001). Conclusion: There was no significant association between metformin treatment and DR among patients with T2DM for >10 years.