2025 Southeastern Residency Conference

Title: Injectable Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Outcomes in Patients Without Diabetes in Outpatient Cardiology Clinics
 
Authors: Kristina Benbow, Madison Burke, Lauren Schultz, Marina Carter, Deborah Hurley, Benjamin Tabor
 
Background: Glucagon-Like Peptide-1 (GLP-1) receptor agonists have emerged as clinically significant treatment options for type 2 diabetes, obesity, and cardiovascular (CV) risk reduction. To date, Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT Trial) is the only trial to comprise of non-diabetic patients with preexisting CV disease defined as myocardial infarction, stroke, or symptomatic peripheral artery disease. In this trial, semaglutide was superior to placebo in reducing a CV composite of death from CV causes, nonfatal myocardial infarction, and nonfatal stroke. This study explores an expansion of the inclusion criteria used in the SELECT Trial, using a large outpatient cardiology population. 
 
Methods: This retrospective cohort study includes adult patients prescribed injectable GLP-1 receptor agonists followed by Prisma Health Cardiology between January 2022 and April 2023. Data was collected through April 2024. Patients were assigned to the control group if they never filled the medication with all other patients considered the intervention group. The primary outcome is a composite of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke. Secondary outcomes include total change in patient health variables (body weight, blood pressure, cholesterol, hemoglobin A1c), hospitalization or urgent medical visit for heart failure, and death from any cause. Descriptive statistics, stratified analyses (control vs intervention group), and multivariable logistic regression will be used to summarize the data and to evaluate the association of GLP-1 use and risk of death and other non-fatal cardiovascular outcomes.
 
Results: 123 patients without diabetes were prescribed a GLP-1 receptor agonist, 83 received the medication (intervention) and 40 did not (control). The primary endpoint did not differ between study arms, with no occurrences of death from CV cause or nonfatal stroke in either group. There was a nonsignificant trend in the control group for nonfatal MI (n=2 control, n=0 intervention; p=0.104). There were no occurrences of death from any cause and hospitalization or urgent medical visit for heart failure between groups. Secondary outcomes reflected a statistically significant reduction for intervention group in body weight (-1.0 kg control, -8.4 kg intervention; p<0.001), BMI (-0.2 kg/m2 control, -3.2 kg/m2 intervention; p<0.001), LDL (+1.4 mg/dL control, -34.1 mg/dL intervention; p<0.001), systolic blood pressure (+1.4 mmHg control; -7.9 mmHg intervention; p<0.001), and diastolic blood pressure (+1.2 mmHg control; -5.4 mmHg intervention; p=0.003). There was no difference in change in A1c between arms (0.0 ± 0.9 control, 0.0 ± 0.3 intervention; p=0.374).

Conclusions: Although unable to find a statistically significant difference in the composite primary endpoint, secondary cardiovascular outcomes favored the use of GLP-1 receptor agonists in patients without diabetes. There was a statistically significant lowering of known cardiovascular risk factors, including body weight, LDL, and blood pressure. Limitations of this study include a small study size which does not allow for true evaluation of primary endpoint, inclusion of patients irrespective of adherence to the GLP-1 receptor agonist or changes to background medications, and lack of available laboratory data points for many patients (notably, A1c and LDL). Unlike the SELECT Trial which looked exclusively at patients with a past medical history of MI, stroke, or symptomatic peripheral artery disease, this study was able to find CV benefit in a population both without CV history and in patients with coronary artery disease, all who were baseline close to having controlled/goal labs and vitals. Ultimately, this data helps advocate for insurance approval of GLP-1 receptor agonist in patients without diabetes secondary to their CV benefit.