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. 2025 Aug;4(8):101995.
doi: 10.1016/j.jacadv.2025.101995. Epub 2025 Jul 18.

Identifying High-Risk Obese Individuals Without Diabetes for GLP-1RA Therapy Using Coronary CTA

Camila V Blair  1 , Daniel Huck  1 , Stephanie A Besser  1 , Rhanderson Cardoso  1 , Arthur Shiyovich  1 , Adam N Berman  2 , David W Biery  1 , Brittany N Weber  1 , Milena Petranovic  3 , Khurram Nasir  4 , Sandeep Hedgire  3 , Jorge Plutzky  1 , Christopher Cannon  1 , Marcelo F Di Carli  3 , Brian B Ghoshhajra  3 , Ludovic Trinquart  5 , Ron Blankstein  6
Affiliations

Identifying High-Risk Obese Individuals Without Diabetes for GLP-1RA Therapy Using Coronary CTA

Camila V Blair et al. JACC Adv. 2025 Aug.

Abstract

Background: The SELECT trial demonstrated that semaglutide reduced major adverse cardiovascular events among individuals with cardiovascular disease (CVD) and overweight/obesity without diabetes. We hypothesized that coronary artery disease (CAD) detected by coronary computed tomography angiography (CCTA) identifies individuals with similar cardiovascular risk.

Objectives: The aim of the study was to evaluate the association between CAD severity by CCTA and cardiovascular outcomes among individuals resembling The SELECT (Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes) trial population but without known CVD.

Methods: We included individuals aged ≥45 years with body mass index ≥27 kg/m2 undergoing CCTA at 2 centers.

Exclusions: prior myocardial infarction, revascularization, stroke, diabetes, end-stage kidney disease, or malignancy. CAD severity was categorized as absent (0%), nonobstructive (1%-49%), or obstructive (≥50%). Extensive nonobstructive CAD was defined as plaque in all coronary arteries. Cox modeling assessed the association between CAD and the composite outcome of cardiovascular death, myocardial infarction, or stroke.

Results: Among 5,173 individuals, 53% were male, and 68% and 62% had hypertension and dyslipidemia, respectively. Individuals with obstructive CAD had a 71% higher risk of events (adjusted HR: 1.71; 95% CI: 1.21-2.42; P = 0.002) vs those with no CAD. At 4 years, event risks were 7.8% for obstructive CAD and 7.7% for extensive nonobstructive CAD, comparable to SELECT's control arm (9.7%). Applying SELECT's relative rate reduction of 20%, the number needed to treat was 66 for obstructive and 67 for extensive nonobstructive CAD, comparable to SELECT's 56.

Conclusions: Obstructive or extensive nonobstructive CAD by CCTA identifies overweight/obese individuals without diabetes and no prior CVD as being at elevated cardiovascular risk, suggesting potential benefit from glucagon-like peptide-1 receptor agonist therapy.

Keywords: coronary CTA; coronary artery disease; obesity; semaglutide.

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Conflict of interest statement

Funding support and author disclosures Dr Huck is supported by the American Heart Association Career Development Award (23CDA1037589). Dr Weber is supported by NIH/NHLBIK23HL159276 and the American Heart Association (21CDA851511). Dr Shiyovich has received honoraria from Pfizer. Dr Petranovic received fellowship support from Novartis (ended July 2024). Dr Weber is supported by Novo Nordisk, Kiniksa, and Oruka. Dr Cannon has received research grants from Amgen, Better Therapeutics, Boehringer-Ingelheim, and Novo Nordisk; salary support from the Colorado Prevention Center (funded by Amgen, Bayer, Cleerly, Esperion, Lexicon, and Silence); consulting fees from Amryt/Chiesi, Amgen, Ascendia, Biogen, Boehringer-Ingelheim, Bristol-Myers Squibb, CSL Behring, Genomadix, Lilly, Janssen, Lexicon, Milestone, Novartis, Pfizer, and Rhoshan; and serves on Data and Safety Monitoring Boards for Areteia, Novo Nordisk, ROMTherapy, Inc, and the U.S. Department of Veterans Affairs. Dr Plutzky serves as a consultant for Altimmune, Amgen, Boehringer Ingelheim, and Novo Nordisk. Dr Blankstein has received research support and consulting fees from Novartis Inc, Amgen Inc, Heartflow Inc, and Nanox AI, and is a consultant for Caristo Inc, and Siemens Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Cardiovascular Death, Myocardial Infarction, or Stroke by Coronary Artery Disease Severity Over 10-Year Follow-Up (A) Kaplan-Meier curves show the 10-year cumulative incidence of the composite outcome (cardiovascular death, myocardial infarction, or stroke) stratified by CAD severity on CCTA: no CAD (blue), nonobstructive CAD (green), and obstructive CAD (red) (log-rank P < 0.001). (B) Bar charts display corresponding event risk at 4 years: 2.0% (no CAD), 3.9% (nonobstructive), and 7.8% (obstructive); and at 10 years: 3.6%, 5.5%, and 11.7%, respectively (P < 0.001), illustrating a stepwise increase in risk with greater CAD severity. CAD = coronary artery disease; CCTA = coronary computed tomography angiography.
Figure 2
Figure 2
Extent of Coronary Artery Disease Among Individuals With Nonobstructive Coronary Artery Disease Kaplan-Meier curves show the 10-year cumulative incidence of the composite outcome (cardiovascular death, myocardial infarction, or stroke) stratified by the number of coronary vessels with nonobstructive plaque (0-4 vessels). The colored lines represent 0 (blue), 1 (green), 2 (yellow), 3 (orange), and 4 (red) involved vessels; log-rank P < 0.001. A stepwise increase in event rates is evident, with extensive nonobstructive CAD (4 vessels) approaching rates observed among patients with obstructive disease. CAD = coronary artery disease.
Central Illustration
Central Illustration
Coronary Computed Tomography Angiography Stenosis Severity May Identify Obese Candidates for Glucagon-Like Peptide-1 Receptor Agonist This illustration compares the randomized SELECT trial (left) in individuals with established cardiovascular disease to a “SELECT-like” cohort from the MGB CCTA registry (right) comprising overweight/obese, nondiabetic patients without prior CVD. Both groups share an age ≥45 years and a BMI ≥27 kg/m2. The composite outcome of cardiovascular death, MI, or stroke occurred at a 9.7% event rate in the SELECT control arm (NNT ≈56) and at 7.8% in those with obstructive CAD on CCTA (NNT ≈66). This highlights how CCTA stenosis severity may help identify high-risk individuals who could derive a similar relative benefit from GLP-1RA therapy. BMI = body mass index; CAD = coronary artery disease; CCTA = coronary computed tomography angiography; CTA = computed tomography angiography; CV = cardiovascular; CVA = cerebrovascular accident; CVD = cardiovascular disease; GLP-1RA = glucagon-like peptide-1 receptor agonist; MGB = Mass General Brigham; MI = myocardial infarction; NNT = number needed to treat; PAD = peripheral artery disease.
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