Coronary Artery Calcium–Guided Risk Stratification and Modeled Cost-Effectiveness of Semaglutide Therapy in Obesity: A US-Based Analysis

Key Highlights

• Higher coronary artery calcium scores were associated with increased rates of major adverse cardiovascular events, heart failure, and all-cause mortality.
• Modeled semaglutide therapy showed lower numbers needed to treat in patients with higher coronary artery calcium burden.
• Incremental cost-effectiveness ratios for semaglutide decreased as coronary artery calcium scores increased but remained above conventional US willingness-to-pay thresholds.

Coronary artery calcium (CAC) scoring may help identify individuals with obesity at higher cardiovascular risk who could derive greater benefit from pharmacologic prevention strategies. In a modeling study published in Diabetes, Obesity and Metabolism, investigators assessed whether CAC-based risk stratification could inform the projected clinical benefit and cost-effectiveness of semaglutide therapy among adults with obesity who met SELECT trial eligibility criteria but had no established cardiovascular disease.

Using real-world registry data combined with Markov-based economic modeling, the authors evaluated associations between CAC burden and cardiovascular outcomes and estimated how these differences translated into modeled numbers needed to treat and incremental cost-effectiveness ratios across CAC strata.

The analysis included 38,058 participants from the CLARIFY registry who underwent CAC screening between 2014 and 2023 and met obesity-related eligibility criteria aligned with the SELECT trial. Participants were stratified into four CAC categories: 0, 1–99, 100–399, and ≥400. Multivariable Cox proportional hazards models were used to estimate associations between CAC category and major adverse cardiovascular events, heart failure, and all-cause mortality.

To model semaglutide benefit, hazard ratios from the SELECT trial were applied to observed event rates. Lifetime Markov models from a US payer perspective were constructed to estimate cost-effectiveness, expressed as incremental cost-effectiveness ratios per quality-adjusted life-year gained, with sensitivity analyses accounting for drug discontinuation and future price reductions.

Study Findings

During a median follow-up of 2.3 years, cardiovascular event rates increased stepwise with higher CAC burden. Compared with CAC = 0, participants with CAC ≥400 had higher adjusted risks of major adverse cardiovascular events (hazard ratio [HR], 1.97), heart failure (HR, 1.76), and all-cause mortality (HR, 1.62).

Modeled semaglutide therapy over 3.3 years yielded a number needed to treat for major adverse cardiovascular events of 151 for CAC = 0 and 34 for CAC ≥400. Similar gradients were observed for heart failure and mortality outcomes. Incremental cost-effectiveness ratios decreased across CAC categories, from approximately $625,863 per quality-adjusted life-year for CAC = 0 to $168,666 per quality-adjusted life-year for CAC ≥400.

Clinical Implications

According to the study authors, these findings suggest that CAC scoring may help identify obese individuals who could experience greater projected clinical benefit and relatively improved economic value from semaglutide therapy. The authors noted that while cost-effectiveness improved with higher CAC burden, modeled ratios remained above commonly cited US willingness-to-pay thresholds at current drug prices.

Expert Commentary

“ … risk stratification using enrollment CAC scores correlated with observed adverse cardiovascular events, the researchers concluded. “Our preliminary evidence suggests that using CAC scores for risk stratification may help guide semaglutide allocation in obese individuals and possibly reduce healthcare costs.”

Reference
Ponnana SR, Zhang T, Sirasapalli SK, et al. Risk stratification using coronary artery calcium and potential benefit of semaglutide therapy: A cost-effectiveness modelling study. Diabetes Obes Metab. 2026;1–9. doi:10.1111/dom.70515