Low-Dose Metformin Linked to Reduced Glaucoma Risk in Patients with Diabetes

A large retrospective cohort study using data from over 723,000 Taiwanese patients with newly diagnosed diabetes mellitus found that lower cumulative doses of metformin were associated with a modestly reduced risk of developing open-angle glaucoma. However, higher doses showed no protective effect. The findings suggest comorbidities such as myopia, cataract and hyperthyroidism may play a more significant role in OAG risk than metformin use alone. Photo: Merck. Click image to enlarge. Open-angle glaucoma (OAG) is recognized as the most prevalent type of glaucoma worldwide and is associated with various contributing factors, including age, sex, race, myopia and diabetes mellitus (DM). Particularly in patients with DM, the use of metformin to control blood sugar has been suspected to affect the development of OAG, but clinical studies have been inconsistent. A new study published in the Journal of Glaucoma investigated this on a large scale in a nationwide database. Its findings suggested that lower dosages of the drug may have a protective effect on OAG risk, but higher doses had no significant impact.This retrospective cohort study included data from over 723,000 patients, aged 20 years or older, from a nationally representative database in Taiwan. All patients had new-onset DM, and were divided into two groups: a metformin-treated group (571,665 patients) and a sulfonylureas-treated group (151,558 patients). Using the Cox proportional hazard researchers evaluated the risk of OAG and metformin treatment after a five-year follow-up period by the cumulative defined daily dose (cDDD), after adjusting for several key risk factors such as sex, age, income, urbanization level, diabetes severity and various comorbidities. A total of 2,102 patients (0.29%) developed OAG within five years of DM diagnosis. Among the metformin group, the incidence rates of OAG were 0.27%, 0.27%, 0.29% and 0.33% with cDDDs of <30, 30 to 120, 120 to 240 and >240, respectively. Following adjustments for relevant variables, patients who received metformin treatment at cDDDs of <30, 30 to 120, 120 to 240, and >240 exhibited hazard ratios (HRs) of 0.81, 0.83, 0.90 and 1.03, respectively, compared with those treated with sulfonylureas.The authors wrote in their paper, “For lower doses (cDDD <30 and 30 to 120), the adjusted HRs (aHRs) indicate a statistically significant protective effect, with risks reduced by approximately 19% and 17%, respectively; however, the upper bounds of the confidence intervals (0.92 and 0.93) approach 1.0, suggesting a weak to moderate strength of this association. At higher doses (cDDD: 120 to 240 and >240), the HRs are closer to or exceed 1.0, with CIs including 1.0, indicating no significant protective effect.”According to the study, the average age of those receiving metformin treatment was 54.98 ± 12.15 years. These patients also had a significantly higher prevalence of certain comorbidities vs. the sulfonylurea-treatment group, including hypertension, hyperlipidemia, COPD and cerebrovascular disease, among others. Particularly hyperthyroidism (aHR=1.77) myopia (aHR=3.04) and cataract (aHR=2.45) were associated with a significantly elevated risk of OAG. Patients aged 65 and older showed a greater risk of OAG compared to those aged 20 to 49 (aHR=1.69).“Due to the fact that aging takes a crucial part in the risk factor for glaucoma progression, those most likely to develop OAG were mainly older men with family histories of OAG, increased intraocular pressure, lean body mass, and cataract history,” the authors wrote in their paper. “According to our results, DM patients with a high DCSI score was closely linked to an increased risk of OAG.”One strength of this study is its population-based approach, as the data is derived from a national database in Taiwan. However, due to the relatively homogeneous population, the results may not be generalizable to other racial or ethnic groups, the authors wrote. “The underlying mechanisms linking cumulative metformin dosage to OAG risk are not yet fully understood, highlighting the need for future prospective clinical trials to assess the potential benefits and risks of metformin treatment for OAG in DM patients,” they concluded in their paper. “Our analysis highlights that comorbidities such as hyperthyroidism, myopia and cataract play a more substantial role in elevating OAG risk compared to DM itself or metformin use. These findings underscore the importance of considering coexisting conditions in the management of OAG risk among DM patients, suggesting that the influence of metformin may be secondary to these underlying factors.”Click here for the journal source. Huang SW Lai YR, Yang Y, Gau SY, Chung NJ, Tsai TH, Huang KH, Lee CY. Association between long-term metformin use and risk of open-angle glaucoma in patients with diabetes mellitus. Journal of Glaucoma. May 16, 2025. [Epub ahead of print.]