Comparative effects of glucagon-like peptide 1 receptor agonists and Metformin on glaucoma risk in patients with type 2 diabetes
Abstract
Purpose To compare effects of glucagon-like peptide 1 (GLP-1) receptor agonists and metformin on the risk of primary open-angle glaucoma (POAG), ocular hypertension, and the need for first-line glaucoma treatments in patients with type 2 diabetes mellitus (T2DM). Design A retrospective cohort study was conducted using electronic medical records data from an international electronic health record network, covering a period from May 2006-2024. Participants Patients with a diagnosis of T2DM who were treated with either GLP-1 receptor agonists or metformin. Methods Data from 120 health care organizations across 17 countries were analyzed. Patient outcomes were assessed at 1, 2, and 3 years. Propensity score matching (PSM) was used to balance covariates such as demographics, comorbidities, and medication use. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Main outcome measures Incidence of POAG, ocular hypertension, and the need for first-line treatments including topical drops and laser trabeculoplasty. Results After PSM, both groups included 61 998 patients at the 1-year follow-up, 27 414 patients at the 2-year follow-up, and 14 100 patients at the 3-year follow-up. Patients treated with GLP-1 receptor agonists showed a significantly decreased risk of POAG development compared with those receiving metformin at 1 year (RR, 0.59; 95% CI, 0.39-0.88), 2 years (RR, 0.50; 95% CI, 0.32-0.78), and 3 years (RR, 0.59; 95% CI, 0.37-0.94). Similar protective effects were observed for ocular hypertension at 1 year (RR, 0.44; 95% CI, 0.31-0.62), 2 years (RR, 0.43; 95% CI, 0.30-0.62), and 3 years (RR, 0.51; 95% CI, 0.34-0.75). The risk of first-line therapy initiation also was lower in the GLP-1 receptor agonists group at 1 year (RR, 0.63; 95% CI, 0.53-0.74), 2 years (RR, 0.71; 95% CI, 0.59-0.85), and 3 years (RR, 0.75; 95% CI, 0.62-0.91). Conclusions Glucagon-like peptide 1 receptor agonists are associated with a significantly lower incidence of POAG, ocular hypertension, and the need for first-line glaucoma treatments compared with metformin in patients with T2DM. These findings highlight the potential ocular benefits of GLP-1 receptor agonists and their expanding role in the clinical management of patients with diabetes. Financial disclosure(s) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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GLP-1RAs have most strongly been linked to a protective effect on glaucoma.
“Within the ophthalmologic space, GLP-1RAs have most strongly been linked to a protective effect on glaucoma.28–30”
From The Effect of Semaglutide and GLP-1 RAs on Risk of Nonarteritic Anterior Ischemic Optic Neuropathy (2025) · cites this paper as [30]
Cites
Kristensen, S. L., Rørth, R., Jhund, P. S., Docherty, K. F., Sattar, N., Preiss, D., Køber, L., Petrie, M. C., & McMurray, J. J. V. (2019) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(19)30249-9 · Cited by 1,663 · see citing works
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Association of semaglutide with risk of suicidal ideation in a real-world cohort
Wang, W., Volkow, N. D., Berger, N. A., Davis, P. B., Kaelber, D. C., & Xu, R. (2024) · Nature Medicine · doi:10.1038/s41591-023-02672-2 · Cited by 248 · see citing works
Reich, N., & Hölscher, C. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.970925 · Cited by 248 · see citing works
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The Effect of Semaglutide and GLP-1 RAs on Risk of Nonarteritic Anterior Ischemic Optic Neuropathy
Abbass, N. J., Nahlawi, R., Shaia, J. K., Allan, K. C., Kaelber, D. C., Talcott, K. E., & Singh, R. P. (2025) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2025.02.025 · Cited by 78 · see citing works
Allan, K. C., Joo, J. H., Kim, S., Shaia, J., Kaelber, D. C., Singh, R., Talcott, K. E., & Rachitskaya, A. V. (2025) · Ophthalmology · doi:10.1016/j.ophtha.2025.01.016 · Cited by 54 · see citing works
Anatriello, A., Liguori, V., Cagnotta, C., Pentella, C., Scavone, C., Capuano, A., & Rinaldi, B. (2026) · Frontiers in pharmacology · doi:10.3389/fphar.2026.1808359 · Cited by 3 · see citing works
“…(Chou et al., 2024; Albargawi et al., 2024; Mahzari et al., 2024; Mayer and Fontelo, 2024; Kick et al., 2024; Lin et al., 2023; Eleftheriadou et al., 2024; Wang et al., 2018; Lin et al., 2024; Hathaway et al., 2024; Cai et al., 2025; Allan et al., 2025; Muayad et al., 2025; Sterling et al., 2023).”
Influential
- Authors
- Muayad, J., Loya, A., Hussain, Z. S., Chauhan, M. Z., Alsoudi, A. F., De Francesco, T., & Ahmed, I. I. K.
- Affiliations
- Texas A&M University (US)
- Baylor College of Medicine (US)
- University of Arkansas for Medical Sciences (US)
- University of Toronto (CA)
- Corresponding author
- Ahmed, Iqbal Ike K.
- ORCID
- Venue
- Ophthalmology
- Publisher
- Elsevier BV
- Published
- 2025-03
- Volume
- 132
- Issue
- 3
- Pages
- 271-279
- ISSN
- 0161-6420 (ISSN-L)
- OpenAlex
- W4401853193
- Cited by
- 45
- References
- 4
- Citations by year
- 2026: 19 · 2025: 20 · 2024: 6
- FWCI
- 17.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Ophthalmology › Drug-Induced Ocular Toxicity
- Keywords
- GLP-1 receptor agonists, metformin, primary open-angle glaucoma, type 2 diabetes, ocular hypertension, glaucoma risk, laser trabeculoplasty, antidiabetic drugs, glaucoma prevention, propensity score matching
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptide-1 Receptor Agonists, Aged, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Glaucoma, Open-Angle, Humans, Hypoglycemic Agents, Intraocular Pressure, Male, Metformin, Middle Aged, Ocular Hypertension, Retrospective Studies, Risk Factors, Trabeculectomy, Incidence, Propensity Score
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