GLP-1 RAs and Cardiovascular and Kidney Outcomes by Body Mass Index in Type 2 Diabetes

Importance The cardiovascular benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may vary by body mass index (BMI), but evidence on BMI-specific outcomes remains limited. Objective To investigate the associations of GLP-1 RA use with cardiovascular and kidney outcomes across BMI categories in patients with type 2 diabetes. Design, Setting, and Participants This retrospective cohort study used the Chang Gung Research Database, a clinical dataset covering multiple hospitals in Taiwan. Patients with type 2 diabetes who received GLP-1 RAs or dipeptidyl peptidase-4 (DPP-4) inhibitors between 2011 and 2022 were identified. DPP-4 inhibitors were selected as the comparator due to their widespread use as a second-line oral hypoglycemic agent and their relatively neutral cardiovascular and kidney effects reported in previous studies. Propensity score matching was applied separately within BMI categories less than 25 and 25 or greater using a comprehensive set of demographic, clinical, and biochemical variables to balance baseline characteristics between treatment groups. The analysis was conducted from December 15, 2023, to July 5, 2024. Exposures Initiation of GLP-1 RAs compared with DPP-4 inhibitors. Main Outcomes and Measures Primary outcomes included major adverse cardiovascular events (MACE; defined as cardiovascular death, myocardial infarction, ischemic stroke, or hospitalization for heart failure) and composite kidney outcomes (defined as estimated glomerular filtration rate decline ≥50% or progression to dialysis). Results Among 97 156 patients with diabetes identified, a total of 7200 matched patients (mean [SD] age, 57.4 [14.2] years; 7473 [51.9%] female) were included (1841 pairs with BMI <25 and 5359 pairs with BMI ≥25). Among patients with BMI 25 or greater, GLP-1 RAs were associated with lower risks of cardiovascular death (hazard ratio [HR], 0.62; 95% CI, 0.46-0.83) and hospitalization for heart failure (subdistribution HR, 0.77; 95% CI, 0.62-0.94). Kidney outcomes were consistent across BMI strata. Restricted cubic spline analysis revealed increasing cardiovascular benefit associated with GLP-1 RAs among patients with higher BMI. Conclusions and Relevance In this cohort study of patients with type 2 diabetes, GLP-1 RAs use was associated with BMI-dependent cardiovascular benefits and consistent kidney protection, suggesting the importance of BMI stratification in guiding treatment decisions.