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

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 2 prescriptions of a GLP-1 RA (semaglutide, dulaglutide, liraglutide, exenatide, tirzepatide, or lixisenatide) at least 6 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 2-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.