Comparative Risk of Glaucoma in Patients Using Sodium-glucose Cotransporter-2 Inhibitors and Metformin: A Multinational Cohort Study

Ssu-Yu Pan; Chien-Hsiang Weng; Shang-Feng Tsai; Yi-Jing Sheen; Jun-Fu Lin; Ching-Heng Lin; I-Jong Wang; Chien-Chih Chou

doi:10.1016/j.ajo.2025.09.027

Comparative Risk of Glaucoma in Patients Using Sodium-glucose Cotransporter-2 Inhibitors and Metformin: A Multinational Cohort Study

Am J Ophthalmol. 2026 Jan:281:333-341. doi: 10.1016/j.ajo.2025.09.027. Epub 2025 Sep 19.

Authors

Ssu-Yu Pan¹, Chien-Hsiang Weng², Shang-Feng Tsai³, Yi-Jing Sheen⁴, Jun-Fu Lin⁵, Ching-Heng Lin⁶, I-Jong Wang⁷, Chien-Chih Chou⁸

Affiliations

¹ From the School of Medicine (S.Y.P., Y.J.S., C.C.C.), College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Ophthalmology (S.Y.P., C.C.C.), Taichung Veterans General Hospital, Taichung, Taiwan.
² Department of Family Medicine (C.H.W.), Brown University Warren Alpert Medical School, Providence, Rhode Island, USA; Brown University Health (C.H.W.), Providence, Rhode Island, USA.
³ Division of Nephrology (S.F.T.), Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine (S.F.T., Y.J.S., C.C.C.), College of Medicine, National Chung Hsing University, Taichung, Taiwan; Department of Life Science (S.F.T.), Tunghai University, Taichung, Taiwan.
⁴ From the School of Medicine (S.Y.P., Y.J.S., C.C.C.), College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Post-Baccalaureate Medicine (S.F.T., Y.J.S., C.C.C.), College of Medicine, National Chung Hsing University, Taichung, Taiwan; Division of Endocrinology and Metabolism (Y.J.S.), Department of Internal Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan; Center for Quantitative Imaging in Medicine (Y.J.S.), Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
⁵ Department of Medical Research (J.F.L., C.H.L.), Taichung Veterans General Hospital, Taichung, Taiwan.
⁶ Department of Medical Research (J.F.L., C.H.L.), Taichung Veterans General Hospital, Taichung, Taiwan; Department of Public Health (C.H.L.), College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; Department of Industrial Engineering and Enterprise Information (C.H.L.), Tunghai University, Taichung, Taiwan; Institute of Public Health and Community Medicine Research Center (C.H.L.), National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁷ Graduate Institute of Biomedical Sciences (I.J.W.), China Medical University, Taichung, Taiwan; Department of Ophthalmology (I.J.W.), National Taiwan University Hospital, Taipei, Taiwan.
⁸ From the School of Medicine (S.Y.P., Y.J.S., C.C.C.), College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Ophthalmology (S.Y.P., C.C.C.), Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine (S.F.T., Y.J.S., C.C.C.), College of Medicine, National Chung Hsing University, Taichung, Taiwan; Department of Ophthalmology (I.J.W.), National Taiwan University Hospital, Taipei, Taiwan. Electronic address: doctorccc@gmail.com.

PMID: 40976317
DOI: 10.1016/j.ajo.2025.09.027

Abstract

Objective: To compare the impact of sodium-glucose cotransporter-2 (SGLT2) inhibitors and metformin on the risk of glaucoma-related outcomes in patients with type 2 diabetes mellitus (T2DM).

Design: Multinational, retrospective clinical cohort study using patient data from 160 healthcare organizations across 21 countries.

Subjects: Adults with T2DM who initiated SGLT2 inhibitors or metformin during 2013-2023 were included.

Intervention: Patients with T2DM prescribed SGLT2 inhibitors were compared to those prescribed metformin. We performed 1:1 propensity score matching to balance age, sex, race, glycated hemoglobin, body mass index, medications, and comorbidities between the SGLT2 inhibitor and metformin groups.

Main outcome measure: The occurrence of ocular hypertension, primary open-angle glaucoma (POAG), and the need for glaucoma medications.

Results: Our final analysis included 32 634 patients prescribed SGLT2 inhibitors and 32 634 prescribed metformin. Compared to metformin, SGLT2 inhibitors are associated with significantly lower risks of ocular hypertension (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.60-0.89), POAG (HR, 0.64; 95% CI, 0.51-0.81), and the need for glaucoma medications (HR, 0.76; 95% CI, 0.69-0.84) in 5 years. These associations remain consistent in patients aged ≥60 years, females, males, Whites, and those prescribed empagliflozin.

Conclusions: Among patients with T2DM, treatment with SGLT2 inhibitors may be associated with lower risks of ocular hypertension, POAG, and the need for glaucoma medications compared to metformin.

Publication types

Multicenter Study
Comparative Study

MeSH terms

Aged
Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / drug therapy
Female
Glaucoma, Open-Angle* / epidemiology
Humans
Hypoglycemic Agents* / therapeutic use
Incidence
Intraocular Pressure / physiology
Male
Metformin* / therapeutic use
Middle Aged
Ocular Hypertension / epidemiology
Propensity Score
Retrospective Studies
Risk Factors
Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

Substances

Metformin
Sodium-Glucose Transporter 2 Inhibitors
Hypoglycemic Agents