Department of Ophthalmology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
JAMA Ophthalmol. 2022 Jul 1;140(7):674-681. doi: 10.1001/jamaophthalmol.2022.1435.
Recent studies suggest that the diabetes drug metformin has a protective effect on open-angle glaucoma (OAG) and age-related macular degeneration (AMD). However, studies have not addressed the critical issue of confounding by indication, and associations have not been evaluated in a large prospective cohort.
To determine the association between diabetes medication and the common eye diseases OAG, AMD, and cataract and to evaluate their cumulative lifetime risks in a large cohort study.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study included participants from 3 independent cohorts from the prospective, population-based Rotterdam Study between April 23, 1990, and June 25, 2014. Participants were monitored for incident eye diseases (OAG, AMD, cataract) and had baseline measurements of serum glucose. Data on diabetes medication use and data from ophthalmologic examinations were gathered.
Type 2 diabetes (T2D) and the diabetes medications metformin, insulin, and sulfonylurea derivatives.
Diagnosis and cumulative lifetime risk of OAG, AMD, and cataract.
This study included 11 260 participants (mean [SD] age, 65.1 [9.8]; 6610 women [58.7%]). T2D was diagnosed in 2406 participants (28.4%), OAG was diagnosed in 324 of 7394 participants (4.4%), AMD was diagnosed in 1935 of 10 993 participants (17.6%), and cataract was diagnosed in 4203 of 11 260 participants (37.3%). Untreated T2D was associated with a higher risk of OAG (odds ratio [OR], 1.50; 95% CI, 1.06-2.13; P = .02), AMD (OR, 1.35; 95% CI, 1.11-1.64; P = .003), and cataract (OR, 1.63; 95% CI, 1.39-1.92; P < .001). T2D treated with metformin was associated with a lower risk of OAG (OR, 0.18; 95% CI, 0.08-0.41; P < .001). Other diabetes medication (ie, insulin, sulfonylurea derivates) was associated with a lower risk of AMD (combined OR, 0.32; 95% CI, 0.18 to 0.55; P < .001). The cumulative lifetime risk of OAG was lower for individuals taking metformin (1.5%; 95% CI, 0.01%-3.1%) than for individuals without T2D (7.2%; 95% CI, 5.7%-8.7%); the lifetime risk of AMD was lower for individuals taking other diabetes medication (17.0%; 95% CI, 5.8%-26.8% vs 33.1%; 95% CI, 30.6%-35.6%).
Results of this cohort study suggest that, although diabetes was clearly associated with cataract, diabetes medication was not. Treatment with metformin was associated with a lower risk of OAG, and other diabetes medication was associated with a lower risk of AMD. Proof of benefit would require interventional clinical trials.
最近的研究表明，糖尿病药物二甲双胍对开角型青光眼（OAG）和年龄相关性黄斑变性（AMD）具有保护作用。然而，这些研究并未解决指示性混杂这一关键问题，并且尚未在大型前瞻性队列中评估相关性。
确定糖尿病药物与常见眼病开角型青光眼、AMD 和白内障之间的关联，并在一项大型队列研究中评估它们的累积终身风险。
设计、地点和参与者：本队列研究纳入了 1990 年 4 月 23 日至 2014 年 6 月 25 日期间，来自前瞻性、基于人群的鹿特丹研究的 3 个独立队列的参与者。参与者被监测是否患有眼部疾病（OAG、AMD、白内障），并进行基线血清葡萄糖测量。收集了关于糖尿病药物使用和眼科检查数据的信息。
2 型糖尿病（T2D）和糖尿病药物二甲双胍、胰岛素和磺酰脲衍生物。
OAG、AMD 和白内障的诊断和累积终身风险。
本研究纳入了 11260 名参与者（平均[标准差]年龄 65.1[9.8]岁；6610 名女性[58.7%]）。2406 名参与者被诊断为 T2D（28.4%），7394 名参与者中有 324 名（4.4%）被诊断为 OAG，10993 名参与者中有 1935 名（17.6%）被诊断为 AMD，11260 名参与者中有 4203 名（37.3%）被诊断为白内障。未经治疗的 T2D 与 OAG（比值比[OR]，1.50；95%置信区间[CI]，1.06-2.13；P=0.02）、AMD（OR，1.35；95%CI，1.11-1.64；P=0.003）和白内障（OR，1.63；95%CI，1.39-1.92；P<0.001）的风险增加相关。用二甲双胍治疗的 T2D 与 OAG（OR，0.18；95%CI，0.08-0.41；P<0.001）的风险降低相关。其他糖尿病药物（即胰岛素、磺酰脲衍生物）与 AMD（合并 OR，0.32；95%CI，0.18-0.55；P<0.001）的风险降低相关。服用二甲双胍的个体发生 OAG 的累积终身风险较低（1.5%；95%CI，0.01%-3.1%），而未患 T2D 的个体为 7.2%（95%CI，5.7%-8.7%）；服用其他糖尿病药物的个体发生 AMD 的终身风险较低（17.0%；95%CI，5.8%-26.8% vs 33.1%；95%CI，30.6%-35.6%）。
本队列研究结果表明，尽管糖尿病与白内障明显相关，但糖尿病药物与白内障无关。用二甲双胍治疗与 OAG 风险降低相关，而其他糖尿病药物与 AMD 风险降低相关。需要进行干预性临床试验来证明其益处。
