Abstract 4362202: Combined associations of GLP-1 medications and healthy lifestyle with cardiovascular outcomes among individuals with diabetes: The Million Veteran Program

Background: Incidence of diabetes in the US has more than doubled in the last 20 years, affecting more than 30 million adults. It is unclear what the combined effect of lifestyle habits and GLP-1 receptor agonists (GLP-1 RAs) has on the risk of cardiovascular outcomes. This study aims to assess the independent and combined impact of protective lifestyle factors and GLP-1 RAs on risk of major cardiovascular events (MACE) in a large cohort of US veterans with diabetes. Methods: A prospective cohort study of individuals with type 2 diabetes within the Million Veteran Program with no previous history of myocardial infarction, stroke, cancers or advanced chronic kidney disease. Risk of MACE (i.e., non-fatal stroke, non-fatal myocardial infarction, cardiovascular death) was assessed in the setting of GLP-1 RA usage and healthy lifestyle habits (healthy eating, physically active, not smoking, restful sleep, no to moderate alcohol intake, good stress management, social connection and support, and no opioid addiction) using Cox proportional hazard regression models. Results: A total of 63,656 participants were included in the study with 418,513 person-years of follow-up. The multivariable-adjusted hazard ratio (HR) of MACE was 0.37 (95% confidence interval (CI): 0.24-0.56) comparing participants adhering to all lifestyle habits to those adopting one lifestyle factor or less. When examined individually, all protective lifestyle factors were significantly and independently associated with a lower likelihood of MACE. Multivariable-adjusted HR of MACE was 0.80 (0.71-0.90) comparing users of GLP-1 RA with those not taking GLP-1 RA. The combination of adherence to healthy lifestyle and use of GLP-1 RAs together was associated with a 50% reduction in MACE compared to veterans with a lower adherence to a healthy lifestyle and no GLP-1 RAs usage with standard diabetes care, HR: 0.50 (95% CI: 0.38-0.65). Conclusions: Healthy lifestyle habits in combination with GLP-1 RAs have a greater association than either therapy alone with reduced risk of MACE emphasizing the importance of lifestyle modification with pharmacotherapy.