GLP-1 Receptor Agonists and Sight-Threatening Ophthalmic Complications in Patients With Type 2 Diabetes
Open accessAbstract
Importance: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with increased risk of diabetic retinopathy (DR) and nonarteritic anterior ischemic optic neuropathy (NAION). The risk of sight-threatening complications associated with GLP-1 RAs is underexamined. Objective: To investigate whether the use of GLP-1 RAs in patients with T2D is associated with the development of DR, NAION, or DR complications. Design, Setting, and Participants: This retrospective cohort study of adults (aged ≥18 years) with T2D and a recent hemoglobin A 1c level of 6.5% or higher was conducted between January 1, 2015, and September 30, 2022, using the TriNetX database. The cohort was divided into 2 groups, adjusted for baseline characteristics through propensity score matching (PSM), based on whether the individuals received prescriptions for a GLP-1 RA. The statistical analysis was conducted on October 10, 2024. Exposures: At least 2 prescriptions of a GLP-1 RA given 6 months apart. Main Outcomes and Measures: Cox proportional hazard regression models were used to evaluate the primary outcome: association between GLP-1 RAs and the risk of incident DR, NAION, or sight-threatening complications over a 2-year follow-up period. Results: After PSM, 185 066 individuals (mean [SD] age, 59.0 [12.5] years; 93 389 females [50.5%]) were prescribed GLP-1 receptor agonists. Use of GLP-1 RAs was associated with an increased incidence of DR (hazard ratio [HR], 1.07; 95% CI, 1.03-1.11), while no statistically significant difference was observed in the risk of NAION (HR, 1.26; 95% CI, 0.94-1.70). In a subgroup analysis of 32 695 patients with preexisting DR, GLP-1 RAs were not associated with progression to proliferative DR (HR, 1.06; 95% CI, 0.97-1.15) or diabetic macular edema (HR, 0.98; 95% CI, 0.95-1.01) but were associated with a lower occurrence of vitreous hemorrhages (HR, 0.74; 95% CI, 0.68-0.80), neovascular glaucoma (HR, 0.78; 95% CI, 0.68-0.88), or blindness (HR, 0.77; 95% CI, 0.73-0.82). Conclusions and Relevance: In this cohort study of individuals with T2D, GLP-1 RA use was associated with a modestly increased risk of incident DR; however, fewer patients experienced sight-threatening DR complications, including blindness, even among those with preexisting DR. These findings suggest that all patients with T2D treated with GLP-1 RAs, regardless of preexisting DR, should be regularly screened and monitored for potential complications of T2D.
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Large observational analyses reported similar 2- to 3-fold risks of NAION with GLP-1 receptor agonists, whereas others observed attenuated or null associations.
“Large observational analyses reported similar 2- to 3-fold risks,2,3,4,5 whereas others observed attenuated or null associations.6,7,8,9”
From New-Onset Nonarteritic Anterior Ischemic Optic Neuropathy and Initiators of Semaglutide in US Veterans With Type 2 Diabetes (2026) · cites this paper as [9]
Studies show conflicting associations between semaglutide or GLP-1 receptor agonists and nonarteritic anterior ischemic optic neuropathy (NAION).
“Studies show conflicting associations.2,3,4,5,6,7,8,9”
From New-Onset Nonarteritic Anterior Ischemic Optic Neuropathy and Initiators of Semaglutide in US Veterans With Type 2 Diabetes (2026) · cites this paper as [9]
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Geroprotective Agents, Including Glucagon-Like Peptide-1 Receptor Agonists, for Ocular Health
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- Authors
- Ramsey, D. J., Makwana, B., Dani, S. S., Patel, M., Panchal, K., Shah, J., Khadke, S., Kumar, A., Patel, T., Kosiborod, M. N., Fonarow, G. C., Ramsey, K. M., Nohria, A., Butler, J., & Ganatra, S.
- Affiliations
- Tufts University (US)
- Lahey Hospital and Medical Center (US)
- Mayo Clinic (US)
- Saint Luke's Hospital (US)
- University of California, Los Angeles (US)
- Northwestern University (US)
- Brigham and Women's Hospital (US)
- University of Mississippi (US)
- Corresponding author
- Ganatra, Sarju
- ORCID
- Venue
- JAMA Network Open
- Publisher
- American Medical Association (AMA)
- Published
- 2025-08-11
- Volume
- 8
- Issue
- 8
- Pages
- e2526321
- ISSN
- 2574-3805 (ISSN-L)
- PMC
- PMC12340654
- OpenAlex
- W4413100686
- Cited by
- 63
- References
- 39
- Citations by year
- 2026: 47 · 2025: 15 · 2024: 1
- FWCI
- 42.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- JAMA Network Open (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Drug-Induced Ocular Toxicity
- Keywords
- GLP-1 receptor agonists, type 2 diabetes, diabetic retinopathy, nonarteritic anterior ischemic optic neuropathy, diabetic macular edema, proliferative diabetic retinopathy, drug safety, adverse drug reactions, retinal detachment, retinal vein occlusion, diabetic cataract, diabetic nephropathy, diabetic retinopathy progression
- MeSH terms
- Glucagon-Like Peptide-1 Receptor Agonists, Aged, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Female, Humans, Hypoglycemic Agents, Male, Middle Aged, Retrospective Studies, Optic Neuropathy, Ischemic
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