Economic modeling of type 2 diabetes (T2D) relies on sets of risk equations (e.g., UKPDS 68) to predict cardiovascular (CV) events and mortality as mediated through changes in risk factors (e.g., HbA1c). Recent CV outcomes trials (CVOTs) have shown significant benefits in events over a short time period (between 2-4 years), along with beneficial changes in risk factors such as blood pressure, HbA1c, and weight. The contributions of these changes to the observed outcomes within these CVOTs are unclear. In patients with high CV risk, the SUSTAIN 6 trial of once-weekly semaglutide+standard of care (SoC) reported a statistically significant reduction in stroke (HR=0.61) after 104 weeks vs. placebo+SoC. We sought to establish the contribution of risk factor changes to this observed outcome, by evaluating the performance of traditional risk equations in predicting outcome benefits seen with once-weekly semaglutide. As a secondary objective, the impact of incorporating the stroke benefit on estimated long term health benefits was assessed. The IQVIA Core Diabetes Model was used to assess predictive accuracy of the UKPDS 68 risk equations on the observed stroke benefit. Secondly, the model was calibrated to preserve the ratio of the observed cumulative incidence of stroke between treatment arms. Finally, results were extrapolated over 50 years. The UKPDS 68 equations were able to predict 64% of the observed 2-year stroke risk reduction, suggesting a drug-mechanistic effect other than changes in risk factors. Calibration results indicate that a relative risk of stroke of 0.83 (17% reduction) applied to once-weekly semaglutide was required to preserve the cumulative incidence ratio. Results of extrapolation increased quality-adjusted life-years by 0.18 and life-years by 0.29 vs. placebo+SoC. Results of this analysis may have implications on future approaches assessing the long term economic impact of new therapies in T2D in this era of multiple CVOTs.


M. Evans: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Novartis AG, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp. P. Johansen: Consultant; Self; Janssen Global Services, LLC.. Employee; Self; Novo Nordisk A/S. H. Vrazic: Employee; Self; Novo Nordisk A/S.

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