Glucagon-Like Peptide-1 Receptor Agonists and Risk of Systemic and Ocular Vascular Complications in Patients With Type 2 Diabetes and Diabetic Retinopathy.
GLP-1 receptor agonists may reduce vascular complications in type 2 diabetes patients with diabetic retinopathy, but further prospective studies are needed to confirm these findings.
Where it sits
this study against the rest of the lixisenatide corpusSummary and findings
The study evaluated the impact of GLP-1 receptor agonists on vascular complications in 173,216 adults with type 2 diabetes and diabetic retinopathy over a 2-year period. GLP-1 RAs were associated with reduced risks of myocardial infarctions, coronary artery procedures, heart failure exacerbations, and various ocular complications. The study used propensity score matching to adjust for baseline characteristics.
Abstract
<h4>Purpose</h4>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.<h4>Design</h4>Retrospective, population-based cohort study.<h4>Participants</h4>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.<h4>Methods</h4>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.<h4>Main outcome measures</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.
Background
This study addresses the question of whether GLP-1 receptor agonists can reduce vascular complications in patients with type 2 diabetes and diabetic retinopathy. Prior research has shown GLP-1 RAs to be effective in managing blood glucose levels, but their impact on vascular outcomes in high-risk groups like those with diabetic retinopathy is less clear. Understanding these effects is crucial as these patients are often excluded from clinical trials.
Methods
The study was a retrospective, population-based cohort analysis using data from the TriNetX research network. It included 173,216 adults with type 2 diabetes and diabetic retinopathy, with a hemoglobin A1c of ≥6.5%. Participants were matched using propensity scores based on whether they received at least 2 prescriptions of a GLP-1 RA, such as lixisenatide, at least 6 months apart. The primary outcomes were macrovascular and microvascular complications, assessed over a 2-year follow-up using Cox proportional hazard regression models.
Results
The study found that patients on GLP-1 RAs had a decreased risk of several vascular complications. Specifically, the hazard ratio for myocardial infarctions was 0.65 (95% CI, 0.61-0.69), and for coronary artery revascularization procedures, it was 0.75 (95% CI, 0.67-0.84). There was also a reduced risk of heart failure exacerbations (HR, 0.78; 95% CI, 0.76-0.81) and acute kidney injuries (HR, 0.68; 95% CI, 0.66-0.71). For ocular complications, the hazard ratio for proliferative diabetic retinopathy was 0.78 (95% CI, 0.71-0.86).
Interpretation
The findings suggest that GLP-1 RAs may confer protective effects against both macrovascular and microvascular complications in patients with type 2 diabetes and diabetic retinopathy. These results align with previous studies showing cardiovascular benefits of GLP-1 RAs, but the specific impact on ocular outcomes is a novel contribution. However, the retrospective design and reliance on database records limit the ability to establish causality. The clinical significance of these findings warrants further investigation in prospective trials.
Key findings
- HR 0.65 for myocardial infarctions, 95% CI 0.61-0.69
- HR 0.75 for coronary artery revascularization, 95% CI 0.67-0.84
- HR 0.78 for heart failure exacerbations, 95% CI 0.76-0.81
- HR 0.68 for acute kidney injuries, 95% CI 0.66-0.71
- HR 0.78 for proliferative diabetic retinopathy, 95% CI 0.71-0.86
Limitations
- retrospective design
- observational study
- 2-year follow-up may not capture long-term effects
- propensity score matching may not fully eliminate bias
- database reliance limits causality assessment