Recent findings from a study published in Ophthalmology compared the effects of glucagon-like peptide-1 (GLP-1) receptor agonists and metformin on the risk of primary open-angle glaucoma (POAG), ocular hypertension (OHT), and the need for first-line glaucoma treatments in patients with type 2 diabetes.
Give me some background.
Type 2 diabetes mellitus (T2DM) is an established risk factor for the development of multiple glaucoma types—including POAG and neovascular glaucoma—mainly due to:
- Microvascular damage
- Neurodegeneration
- Metabolic abnormalities secondary to chronic hyperglycemia
However: The authors of this research noted that the association between oral antihyperglycemic agents, such as metformin and GLP-1 receptor agonists, and glaucoma in diabetic patients remains poorly understood.
Bring it back to this study.
Previous studies have suggested that GLP-1 receptor agonists may offer protective benefits against glaucoma development through their neuroprotective and anti-inflammatory properties.
Consequently: This study compared the efficacy of GLP-1 receptor agonists with metformin, as these agents have the potential to reduce oxidative stress and enhance cellular survival pathways, which could lower intraocular pressure (IOP) and protect retinal ganglion cells.
Talk about the study.
In this retrospective cohort study, investigators utilized real-world data from TriNetX—an international electronic health record (EHR) network—covering a period from May 2006 to May 2024.
Researchers analyzed data from 120 healthcare organizations across 17 countries, and patient outcomes were assessed at 1, 2, and 3 years.
They also used propensity score matching (PSM) to balance covariates such as demographics, comorbidities, and medication usage.
Anything else?
Patients diagnosed with T2DM who were treated with either GLP-1 receptor agonists or metformin were included in the study.
The main outcome measures included the incidence of:
- POAG
- OHT
- The need for first-line treatments, such as
- Beta-blockers
- Prostaglandin analogs
- Brimonidine
- Brinzolamide
- Dorzolamide
- Netarsudil
- Laser trabeculoplasty
Findings?
After PSM, both GLP-1 receptor agonists and metformin groups included:
- 1-year follow-up: 61,998 patients
- 2-year follow-up: 27,414 patients
- 3-year follow-up: 14,100
Patients treated with GLP-1 receptor agonists had a significantly decreased risk of developing POAG compared to those on metformin:
- 41% at 1 year (risk ratio [RR] 0.59, 95% confidence interval [CI] 0.39-0.88)
- 50% at 2 years (RR 0.50, 95% CI 0.32-0.78)
- 41% at 3 years (RR 0.59, 95% CI 0.37-0.94)
Similar protective effects were observed for OHT, with risk reductions of:
- 56% at 1 year (RR 0.44, 95% CI 0.31-0.62)
- 57% at 2 years (RR 0.43, 95% CI 0.30-0.62)
- 49% at 3 years (RR 0.51, 95% CI 0.34-0.75)
What about the risk of initiating first-line treatments?
The risk of first-line therapy initiation was also lower in the GLP-1 receptor agonists group at:
- 37% at 1 year (RR 0.63, 95% CI 0.53-0.74)
- 29% at 2 years (RR 0.71, 95% CI 0.59-0.85)
- 25% at 3 years (RR 0.75, 95% CI 0.62-0.91)
Take home.
These findings suggest that GLP-1 receptor agonists are associated with a significantly lower incidence of POAG, OHT, and the need for first-line glaucoma treatments compared to metformin in patients with type 2 diabetes.