Amelia Jones | 15/05/2026
HEOR is proud to have co-authored the Journal of Medical Economics’ most cited and viewed article of 2025, “Cost-effectiveness of semaglutide in people with obesity and cardiovascular disease without diabetes”.
HEOR co-authors Phil McEwan (CEO), Volker Foos (Technical Director, Health Economics), and Florian Yeates (Health Economist) provide commentary on the methodological approach used in the analysis.
Advancing modelling approaches in obesity and cardiovascular disease
This study applies a modelling framework that incorporates direct clinical outcomes from the SELECT trial to evaluate long-term health and economic impacts in adults with overweight or obesity and established cardiovascular disease, without type 2 diabetes.
A key feature of the approach is the use of observed cardiovascular event data rather than relying on surrogate risk factors. By grounding the model in trial-derived outcomes, the analysis aims to more directly reflect the relationship between treatment and clinically meaningful endpoints.
Integrating multiple disease pathways
The model brings together several related disease processes within a single analytical framework. Time-to-event survival equations derived from trial data are used to estimate major cardiovascular outcomes, while additional components capture progression to type 2 diabetes and chronic kidney disease.
These pathways are incorporated into a Markov model structure based on patient-level data, allowing interactions between cardiovascular, metabolic, and renal outcomes to be assessed over time. This integrated approach differs from models that consider these outcomes in isolation.
Use of trial-based evidence and extrapolation
Clinical outcomes are estimated directly from SELECT trial data and extrapolated beyond the trial period using parametric survival modelling techniques. This enables the analysis of longer-term outcomes while maintaining consistency with observed trial results.
The model also incorporates treatment discontinuation using trial-based rates and applies assumptions regarding post-discontinuation effects, including weight regain and changes in treatment benefit. These elements are included to reflect treatment patterns and their potential impact on long-term outcomes.
Contextualising outcomes within decision frameworks
Results from the model are interpreted using established economic and clinical value frameworks, including incremental cost-effectiveness ratios and the ACC/AHA value framework. This allows outputs to be considered within commonly used US decision-making contexts without reliance on a single metric.
Methodological contribution and future application
The study illustrates an approach to modelling obesity pharmacotherapy that prioritises direct clinical endpoints and integrated disease pathways. By linking cardiovascular, metabolic, and renal outcomes within a unified framework, the analysis provides an example of how multiple dimensions of disease burden can be captured in economic evaluation.
This approach may be applicable to future analyses of therapies in obesity and related conditions. Areas for further methodological development include the incorporation of real-world evidence, long-term treatment adherence, and refinement of assumptions around discontinuation and disease progression.