Semaglutide becomes significantly more cost-effective for people with higher coronary artery calcium scores, suggesting calcium scoring could help target who should receive this expensive therapy.
NNT drops from 151 to 34People with the highest coronary calcium scores need far fewer patients treated to prevent one major heart event with semaglutide
What the researchers found
People with coronary artery calcium scores of ≥400 had nearly double the risk of major cardiovascular events compared to those with scores of 0 (HR: 1.97). When modelling 3.3 years of semaglutide therapy, the number needed to treat to prevent one major cardiovascular event dropped from 151 for CAC=0 to just 34 for CAC≥400. The incremental cost-effectiveness ratio also improved dramatically: $625,863/QALY for CAC=0 versus $168,666/QALY for CAC≥400, though neither crossed the traditional willingness-to-pay threshold.
Why it matters
Semaglutide costs thousands of dollars per year, making it impractical to prescribe to every obese patient. This study provides a practical framework for using a simple, widely available test — coronary calcium scoring — to identify the patients who would get the most bang for the buck, potentially making the case for insurance coverage in high-risk groups.
How the study worked
The researchers used CAC scores from 38,058 participants in the CLARIFY registry who met SELECT trial criteria. Participants were stratified into four calcium score groups (0, 1-99, 100-399, ≥400). Multivariable Cox proportional hazard models estimated cardiovascular event risk across groups, and lifetime Markov models simulated semaglutide therapy outcomes to calculate number needed to treat and cost-effectiveness ratios.
What this study cannot tell us
This is a modelling study, not a randomized trial, so the cost-effectiveness estimates depend on assumptions that may not hold in practice. The CLARIFY registry population may not be representative of all obese individuals. Even the best-case scenario (CAC≥400) still produced an ICER above the commonly used $100,000/QALY willingness-to-pay threshold. Real-world adherence and drug pricing changes could significantly alter results.
How to read the evidence
This is a modelling study based on registry data, not a randomized controlled trial. While the underlying data are robust (38,000+ participants), the cost-effectiveness projections depend on model assumptions and require clinical validation.
When this study was published
Published in 2026, this is a very current analysis that builds on the landmark SELECT trial data, making it highly relevant to ongoing debates about GLP-1 drug coverage and patient selection.
The bigger picture
As GLP-1 receptor agonists like semaglutide strain healthcare budgets worldwide, identifying which patients benefit most becomes critical. This study adds to a growing body of work exploring precision medicine approaches to obesity treatment — using existing risk tools to allocate expensive therapies where they'll have the greatest impact.
Questions still open
- At what drug price point would semaglutide become cost-effective even for lower CAC score groups?
- Could combining CAC scores with other biomarkers further improve patient selection for GLP-1 therapy?
- How would generic semaglutide or biosimilar competition change these cost-effectiveness calculations?
Common questions
What is a coronary artery calcium score and how does it relate to semaglutide?
Is semaglutide cost-effective for everyone with obesity?
Read the original research
Risk stratification using coronary artery calcium and potential benefit of semaglutide therapy: A cost-effectiveness modelling study.
Diabetes, obesity & metabolism
Citation
Ponnana, Sai Rahul; Zhang, Tong; Sirasapalli, Santosh Kumar; Chen, Zhuo; Dazard, Jean-Eudes; Surya, Niketh; Elhussain, Shamsa; Sivanantham, Kanimozhi; Okyere, Robert; Neeland, Ian J; Rajagopalan, Sanjay; Deo, Salil V. (2026). Risk stratification using coronary artery calcium and potential benefit of semaglutide therapy: A cost-effectiveness modelling study.. Diabetes, obesity & metabolism. https://doi.org/10.1111/dom.70515