Abstract 4367419: Glucagon-Like Peptide-1 Receptor Agonist Use Is Associated With Lower Risk Of Cardiovascular Event Recurrence Compared With Use Of Bupropion-Naltrexone or Phentermine-Topiramate: A Nationwide Target Trial Emulation Study

Introduction: The Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT) trial showed that the glucagon-like peptide-1 receptor agonist (GLP1-RA) semaglutide was effective versus placebo for the secondary prevention of atherosclerotic cardiovascular disease. However, the comparative effectiveness of GLP-1RA versus other FDA-approved antiobesity medications (bupropion-naltrexone [BN] and phentermine-topiramate [PT]) has not been evaluated. Research Objective/Aims: To determine the association between GLP1-RA prescription versus BN or PT prescription and recurrent cardiovascular events. Methods: This was a nationwide, retrospective, observational study with an incident user, target trial emulation design which used Truveta electronic health record data. Participants with a history of stroke or myocardial infarction, overweight/obesity, and without diabetes mellitus were included. The primary end point was time to first recurrent CVD event (stroke/MI), using an algorithm relying on a combination of diagnosis, laboratory, and procedure data. Secondary end points included change in cardiovascular risk factors. A post-hoc sensitivity analysis using only diagnosis data to classify stroke/MI events was also performed. Propensity score overlap weighting was used to balance the characteristics of patients across treatment groups (Figure 1). Results: In the GLP-1RA vs. BN comparison for the primary endpoint, 16,559 received a GLP-1RA and 18,751 received BN; in the GLP-1RA vs. PT comparison, 16,673 received BN and 10,397 received PT. Descriptive characteristics of the study population are shown in Figure 1. Unadjusted survival curves are shown in Figure 2. GLP-1RA use was associated with lower risk of stroke/myocardial infarction compared to BN (HR 0.42, 95% CI 0.31-0.57, before adjustment; aHR 0.60, 95% CI 0.42-0.85 after overlap weighting, p=0.004), and compared to PT (HR 0.40, 95% CI 0.29-0.56, aHR 0.60, 95% CI 0.41-0.88, p=0.009). A sensitivity analysis for a more sensitive and less specific definition of stroke/MI yielded similar results. Secondary endpoints for change in BMI, lipid levels, and glycated hemoglobin also showed greater improvement in these biomarkers for patients exposed to GLP-1RA as shown in Figure 3. Conclusions: Among patients with CVD, overweight/obesity, and without diabetes mellitus, prescription of GLP-1RA was associated with lower risk of recurrent cardiovascular events compared to approved oral antiobesity therapies.