Abstract 4370661: Cardiovascular Benefits of GLP-1 Receptor Agonists in Non-Obese Patients With Type 2 Diabetes, Chronic Kidney Disease, or Coronary Artery Disease: A Real-World TriNetX Analysis

Background: GLP-1 receptor agonists (GLP-1 RAs), originally approved for glycemic control and weight management in type 2 diabetes (T2D), have demonstrated cardiovascular (CV) benefit in obese populations. However, their effectiveness in non-obese patients remains unclear. We aimed to evaluate the association between GLP-1 RA use and cardiovascular outcomes in non-obese patients with T2D, chronic kidney disease (CKD), or coronary artery disease (CAD). Methods: We conducted a retrospective, observational cohort study using the TriNetX research network. Adults (>18 years) with a BMI <30 kg/m2 and a diagnosis of T2D, CKD, or CAD who were hospitalized for acute exacerbations between 2017 and 2024 were included. Patients treated with GLP-1 RAs were propensity score–matched 1:1 to untreated controls based on 28 covariates including demographics, comorbidities, and baseline medications. The primary outcome was a composite of all-cause mortality, myocardial infarction (MI), stroke, and heart failure (HF) at 1 and 5 years. Results: We identified 18,397 non-obese T2D patients, 1,446 CKD patients, and 2,299 CAD patients treated with GLP-1 RAs. The mean age was 63 years (SD 10) for T2D, 66 years (11) for CKD, and 63 years (10) for CAD patients. Males comprised 59% of the T2D, 48% of the CKD, and 59% of the CAD cohorts. At 1 year, GLP-1 RA treatment was associated with a 48% reduction in the composite outcome in T2D patients (HR 0.52; 95% CI [0.47–0.58]), 58% reduction in CKD patients (HR 0.42; 95% CI [0.34–0.53]), and 36% reduction in CAD patients (HR 0.64; 95% CI [0.54–0.77]). The beneficial effect of GLP-1 RAs remained at 5 years across all phenotypes (T2D HR 0.55, 95% CI[0.51-0.59] ; CKD HR 0.55, 95% CI[0.45-0.66]; CAD HR 0.69, 95% CI[0.59-0.79]). Conclusions: In this large real-world cohort of non-obese patients with cardiometabolic conditions, GLP-1 RA treatment was associated with significantly improved cardiovascular outcomes, with the most pronounced benefit in CKD patients. These findings suggest that GLP-1 RAs offer cardiovascular protection independent of weight loss and support their broader use beyond obesity-focused indications.