Coronary CT scans can identify overweight or obese individuals without diabetes or known heart disease who have cardiovascular risk levels similar to those who benefited from semaglutide in the SELECT trial.
71% higher cardiovascular riskObese individuals with obstructive coronary artery disease on CT had significantly elevated risk, comparable to the SELECT trial population that benefited from semaglutide
What the researchers found
Among 5,173 individuals with BMI ≥27, those with obstructive coronary artery disease (≥50% blockage) had a 71% higher risk of cardiovascular events compared to those with no disease (adjusted HR: 1.71; 95% CI: 1.21-2.42; P = 0.002). At 4 years, event rates were 7.8% for obstructive CAD and 7.7% for extensive nonobstructive CAD — comparable to the 9.7% rate in the SELECT trial's control arm. The estimated number needed to treat with semaglutide was 66-67, close to SELECT's 56.
Why it matters
The SELECT trial proved semaglutide reduces cardiovascular events in obese people with established heart disease but without diabetes. However, many people at high cardiovascular risk don't have a diagnosed heart condition yet. This study shows that a common imaging test — coronary CT angiography — can identify these hidden high-risk individuals, potentially expanding the population who could benefit from GLP-1 receptor agonist therapy.
How the study worked
This was a retrospective cohort study of 5,173 adults aged 45 or older with BMI ≥27 who underwent coronary CT angiography at two medical centers. Researchers excluded those with prior heart attack, revascularization, stroke, diabetes, end-stage kidney disease, or cancer. They categorized coronary artery disease severity and used Cox regression models to assess the relationship between disease severity and cardiovascular outcomes (death, heart attack, or stroke).
What this study cannot tell us
This was a retrospective study, so it cannot prove that semaglutide would actually reduce events in the identified population — only a randomized trial could confirm that. The number needed to treat was estimated by applying SELECT trial effect sizes, not from actual treatment data. The study population came from two academic centers, which may not represent broader populations. Selection bias exists since participants had clinical reasons for getting CT scans.
How to read the evidence
This is a large retrospective cohort study from two academic centers. While it provides strong observational evidence with specific risk estimates, it cannot establish causation or directly prove treatment benefit — projected treatment effects are extrapolated from a separate trial.
When this study was published
Published in 2025, this study directly builds on the landmark 2023 SELECT trial results and represents current thinking on expanding GLP-1RA therapy to new patient populations.
The bigger picture
GLP-1 receptor agonists like semaglutide are transforming obesity and cardiovascular medicine, but questions remain about which patients benefit most. This study adds an imaging-based approach to patient selection, suggesting that subclinical coronary disease detected on CT could serve as a gateway to preventive peptide therapy — even in people who don't yet have symptoms or a cardiovascular diagnosis.
Questions still open
- Should routine coronary CT screening be considered for obese individuals to identify candidates for GLP-1 receptor agonist therapy?
- Would a randomized trial of semaglutide in this CT-identified population confirm the projected cardiovascular benefit?
- How does the cost-effectiveness of CT screening plus semaglutide treatment compare to other cardiovascular prevention strategies in obese patients?
Common questions
What is semaglutide and why is it relevant to heart health?
What is coronary CT angiography and how does it help?
Read the original research
Identifying High-Risk Obese Individuals Without Diabetes for GLP-1RA Therapy Using Coronary CTA.
JACC. Advances, 4(8), 101995
Citation
Blair, Camila V; Huck, Daniel; Besser, Stephanie A; Cardoso, Rhanderson; Shiyovich, Arthur; Berman, Adam N; Biery, David W; Weber, Brittany N; Petranovic, Milena; Nasir, Khurram; Hedgire, Sandeep; Plutzky, Jorge; Cannon, Christopher; Di Carli, Marcelo F; Ghoshhajra, Brian B; Trinquart, Ludovic; Blankstein, Ron. (2025). Identifying High-Risk Obese Individuals Without Diabetes for GLP-1RA Therapy Using Coronary CTA.. JACC. Advances, 4(8), 101995. https://doi.org/10.1016/j.jacadv.2025.101995