Glucagon-Like Peptide-1 Receptor Agonists and Risk of Systemic and Ocular Vascular Complications in Patients with Type 2 Diabetes and Diabetic Retinopathy

Apr 23, 2026American journal of ophthalmology

Glucagon-Like Peptide-1 Drugs and Risk of Body and Eye Blood Vessel Problems in Type 2 Diabetes with Diabetic Eye Disease

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Abstract

Among 30,613 adults with type 2 diabetes and diabetic retinopathy, those prescribed GLP-1 receptor agonists had a significantly reduced risk of various complications.

Patients on GLP-1 receptor agonists had a 35% lower risk of myocardial infarctions compared to those not on these medications.
There was a 25% reduction in the need for coronary artery revascularization procedures in patients using GLP-1 receptor agonists.
Heart failure exacerbations decreased by 22% in individuals prescribed GLP-1 receptor agonists.
The risk of ischemic strokes was reduced by 22% among patients taking GLP-1 receptor agonists.
Patients experienced a 22% lower risk of lower extremity amputations and a 32% reduced risk of acute kidney injuries.
Fewer individuals progressed to proliferative diabetic retinopathy with a 22% reduction in risk associated with GLP-1 receptor agonists.

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PURPOSE: To evaluate the association of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) use on macrovascular and microvascular outcomes in patients with type 2 diabetes (T2D) and diabetic retinopathy (DR)-a high-risk group often excluded from clinical trials.

DESIGN: Retrospective, population-based cohort study.

PARTICIPANTS: Adults aged ≥18 years with T2D (with hemoglobin A1c of ≥6.5%) and a pre-existing diagnosis of DR from the TriNetX research network database between January 1, 2015, and December 31, 2022.

METHODS: The study included 173,216 adults with T2D, all of whom had DR, adjusted for baseline characteristics through propensity score matching (PSM) based on whether the individuals received at least two prescriptions of a GLP-1 RA (semaglutide, dulaglutide, liraglutide, exenatide, tirzepatide, or lixisenatide) at least six months apart.

MAIN OUTCOME MEASURES: Cox proportional hazard regression models were used to evaluate the association between GLP-1 RAs and the risk of incident macrovascular and microvascular complications over a two-year follow-up period.

RESULTS: After PSM, 30,613 individuals (mean [SD] age, 61.6 [11.4] years; 53.2% were females) were prescribed GLP-1 RAs. Patients on GLP-1 RAs had a decreased risk of myocardial infarctions (MIs; hazard ratio [HR], 0.65; 95% CI, 0.61-0.69), coronary artery revascularization procedures (HR, 0.75; 95% CI, 0.67-0.84), heart failure exacerbations (HR, 0.78; 95% CI, 0.76-0.81), ischemic strokes (HR, 0.78; 95% CI, 0.74-0.83), lower extremity amputations (HR, 0.78; 95% CI, 0.69-0.88), acute kidney injuries (AKI; HR, 0.68; 95% CI, 0.66-0.71), or the need for renal replacement therapy (RRT; HR, 0.40; 95% CI, 0.36-0.43). Fewer individuals also progressed to proliferative diabetic retinopathy (HR, 0.78; 95% CI, 0.71-0.86), experienced retinal vein occlusions (RVOs; HR, 0.70; 95% CI, 0.61-0.80), or developed neovascular glaucoma (HR, 0.65; 95% CI, 0.47-0.89); no association was observed for retinal artery occlusions (RAOs; HR, 0.85; 95% CI, 0.57-1.26) or cases of non-arteritic ischemic optic neuropathy (NAION; HR, 0.88; 95% CI, 0.54-1.44).

CONCLUSIONS: In patients with T2D and pre-existing DR, the use of GLP-1 RAs was associated with a reduced risk of major macrovascular and microvascular complications, including those directly affecting the retina. Future studies are needed to assess the extent to which GLP-1 RAs benefit long-term outcomes.

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Glucagon-Like Peptide-1 Receptor Agonists and Risk of Systemic and Ocular Vascular Complications in Patients with Type 2 Diabetes and Diabetic Retinopathy

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