GLP-1 receptor agonist use was associated with lower risk in adults with type 2 diabetes and cardiovascular risk factors, without a detectable difference.
Evidence
This retrospective TriNetX propensity-matched cohort study compared 350,536 GLP-1 RA users with 350,536 nonusers and found lower legal blindness hazards at 1, 3, and 5 years but no significant ION difference at those time points.
Caveat
The evidence comes from de-identified observational EMR data and univariable survival analyses, so residual confounding and coding limitations may affect the association.
Simplified
PURPOSE: To evaluate whether glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy influences the risk of and (ION) among patients with type 2 diabetes mellitus (T2DM) and cardiovascular risk factors (CVRF).
DESIGN: A retrospective cohort study using de-identified electronic medical record (EMR) data from TriNetX, encompassing 72 healthcare organizations across the United States between January 2018 and January 2025.
PARTICIPANTS: Adults (≥18 years) with T2DM (A1c <10%) and at least one CVRF (hyperlipidemia, essential hypertension, overweight/obesity, or chronic ischemic heart disease) who were prescribed or not prescribed a GLP-1 RA.
METHODS: Patients with type 1 diabetes, optic neuritis, giant cell arteritis, or phosphodiesterase-5 inhibitor use were excluded. GLP-1 RA users were required to have ≥2 prescription records. A 1:1 propensity score matching (PSM) was performed to balance demographics, comorbidities, laboratory values, and concurrent antidiabetic medications. Outcomes were assessed at 1-, 3-, and 5-year follow-ups. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using univariable survival analyses.
MAIN OUTCOME MEASURES: Incidence of legal blindness and ischemic optic neuropathy.
RESULTS: After PSM, each cohort included 350,536 patients (mean age 58.7 ± 12.6 years; 61.6% female). GLP-1 RA use was associated with a significantly reduced risk of legal blindness at 1 year (HR 0.589, 95% CI 0.476-0.728), 3 years (HR 0.677, 95% CI 0.583-0.788), and 5 years (HR 0.669, 95% CI 0.583-0.768). There was no significant difference in ION incidence between cohorts at 1 year (HR 0.872, 95% CI 0.627-1.212), 3 years (HR 1.002, 95% CI 0.792-1.268), or 5 years (HR 0.978, 95% CI 0.789-1.211).
CONCLUSION: GLP-1 receptor agonist therapy was associated with a significantly lower risk of legal blindness and no difference in ION incidence. These findings indicate potential ocular benefits of GLP-1 RAs beyond glycemic and cardiovascular outcomes.
Key numbers
0.589
Decrease in Risk (1-Year)
Hazard Ratio for at 1-year follow-up
0.677
Decrease in Risk (3-Year)
Hazard Ratio for at 3-year follow-up
0.669
Decrease in Risk (5-Year)
Hazard Ratio for at 5-year follow-up
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