Relative Impact of GLP-1 Agonist Use on Microvascular Versus Macrovascular Complications

Background: Diabetes and obesity contribute to vascular complications. The effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on microvascular and macrovascular outcomes in the general population remain less well understood. Objective: To compare the adjusted odds of microvascular and macrovascular complications among adults in the United States (US) using GLP-1 RAs. Methods: We conducted a survey-weighted logistic regression analysis using National Health and Nutrition Examination Survey (NHANES) data from 2011-2018. Microvascular complications were defined as albuminuria or diabetic retinopathy, while macrovascular complications included myocardial infarction, stroke, or coronary artery disease. Models adjusted for demographic, socioeconomic, and clinical factors. Results: In the adjusted models, the use of GLP-1 RA was linked to increased odds of microvascular complications (OR 2.29, 95% CI 1.05-4.97, p=0.037). No significant association was observed with macrovascular complications (OR 1.27, 95% CI 0.65-2.51, p=0.478). Established risk factors, including older age, higher BMI, lower income, and smoking, were independently associated with higher odds of vascular complications. Conclusion: The use of GLP-1 RAs was linked to increased odds of microvascular complications following adjustment for the confounders, even as no significant association was reported with macrovascular complications. This possibly reflects confounding through indication, given that such medications/agents are mainly prescribed to persons with either longer duration or increasingly severe diabetes. These findings indicate the need for longitudinal studies to explain the temporal correlations between the use of GLP-1 RA and complication risk.