Comparative Effects of Glucagon-like Peptide 1 Receptor Agonists and Metformin on Glaucoma Risk in Patients with Type 2 Diabetes.

Abstract

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). 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. Patients with a diagnosis of T2DM who were treated with either GLP-1 receptor agonists or metformin. 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. Incidence of POAG, ocular hypertension, and the need for first-line treatments including topical drops and laser trabeculoplasty. 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). 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. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.