Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Aug 1;8(8):e2526321.
doi: 10.1001/jamanetworkopen.2025.26321.

GLP-1 Receptor Agonists and Sight-Threatening Ophthalmic Complications in Patients With Type 2 Diabetes

David J Ramsey  1   2   3 , Bhargav Makwana  4 , Sourbha S Dani  5 , Manav Patel  5 , Krisha Panchal  5 , Jui Shah  4 , Sumanth Khadke  4 , Ashish Kumar  6 , Tirth Patel  5 , Mikhail N Kosiborod  7 , Gregg C Fonarow  8 , Kathryn Moynihan Ramsey  9 , Anju Nohria  10 , Javed Butler  11   12 , Sarju Ganatra  5
Affiliations

GLP-1 Receptor Agonists and Sight-Threatening Ophthalmic Complications in Patients With Type 2 Diabetes

David J Ramsey et al. JAMA Netw Open. .

Abstract

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 A1c 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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr D.J. Ramsey reported receiving personal fees from Regeneron Pharmaceuticals and Beaver-Visitec International Inc outside the submitted work. Dr Kosiborod reported receiving institutional support from grants from AstraZeneca, Boehringer Ingelheim, and Pfizer; personal fees from AstraZeneca, Boehringer Ingelheim, Pfizer, 35Pharma, Alnylam, Amgen, Applied Therapeutics, Arrowhead Pharmaceuticals, Bayer, Corcept Therapeutics, Cytokinetics, Dexom, Eli Lilly, Esperion Therapeutics, Imbria Therapeutics, Janssen, Lexicon Pharmaceuticals, Merck, NoroNordisk, Pharmacosmos, Regeneron Pharmaceuticals, Roche, Sanofi, scPharmaceuticals, Structure Therapeutics, Vifor Pharma, and Youngene Therapeutics; stock options held in Artera Health and Saghmos Therapeutics; and salary from AstraZeneca Research and Development outside the submitted work. Dr Fonarow reported receiving personal fees from Abbot, AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer outside the submitted work. Dr Nohria reported receiving personal fees from AstraZeneca and Takeda Oncology and grants from Bristol Myers Squibb outside the submitted work. Dr Butler reported receiving personal fees from Abbott, Adaptyx, American Regent, Amgen, AskBio, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimension, Cardior, CSL Vifor, CVRx, Cytokinetics, Daxor, Diastol, Edwards, Element Sciences, Faraday, Idorsia, Impulse Dynamics, Imbria, Innolife, Intellia, Inventiva, Levator, Lexicon, Eli Lilly, Mankind, Medtronic, Merck, New Amsterdam, Novartis, NovoNordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Pulnovo, Regeneron Pharmaceuticals, Renibus, Reprieve, Roche, Rycarma, Saillent, Salamandra, Salubris, scPharmaceuticals, SQ Innovation, Secretome, Sequanna, Transmural, TekkunLev, Tenex, Tricog, Ultromic, Vera, and Zoll outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Ophthalmic End Points and Development of Sight-Threatening Complications in Patients With Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) Prescriptions
Outcomes in the entire cohort (n = 185 066 individuals per group) are shown in blue, while outcomes for the subgroup with preexisting diabetic retinopathy (DR) (n = 32 695 individuals per group) are shown in orange. Marker size is proportional to the mean total number of events in each category. DME indicates diabetic macular edema; NAION, nonarteritic anterior ischemic optic neuropathy; PDR, proliferative diabetic retinopathy; and VEGF, vascular endothelial growth factor.
See this image and copyright information in PMC

References

    1. Husain M, Birkenfeld AL, Donsmark M, et al. ; PIONEER 6 Investigators . Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019;381(9):841-851. doi: 10.1056/NEJMoa1901118 - DOI - PubMed
    1. Wilding JPH, Batterham RL, Calanna S, et al. ; STEP 1 Study Group . Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. doi: 10.1056/NEJMoa2032183 - DOI - PubMed
    1. Kristensen SL, Rørth R, Jhund PS, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019;7(10):776-785. doi: 10.1016/S2213-8587(19)30249-9 - DOI - PubMed
    1. Tuttle KR, Bain SC, Bosch-Traberg H, et al. Effects of once-weekly semaglutide on kidney disease outcomes by KDIGO risk category in the SUSTAIN 6 trial. Kidney Int Rep. 2024;9(7):2006-2015. doi: 10.1016/j.ekir.2024.04.028 - DOI - PMC - PubMed
    1. Patel R, Wadid M, Makwana B, et al. GLP-1 receptor agonists among patients with overweight or obesity, diabetes, and HFpEF on SGLT2 inhibitors. JACC Heart Fail. 2024;12(11):1814-1826. doi: 10.1016/j.jchf.2024.07.006 - DOI - PubMed

MeSH terms

Substances