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

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.