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

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. To determine the association between GLP1-RA prescription versus BN or PT prescription and recurrent cardiovascular events. 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 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 Unadjusted survival curves are shown in 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 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.

Duke Scholars

Author Brian C. Mac Grory Neurology, Stroke and Vascular Neurology