Estimating cardiovascular disease-free life-years with the addition of semaglutide in people with type 2 diabetes using pooled data from SUSTAIN 6 and PIONEER 6

Abstract Introduction Cardiovascular disease (CVD) is the leading cause of disability and death in people with type 2 diabetes (T2D). In a post hoc analysis of pooled data (POOLED cohort) from two phase 3, randomized CV outcomes trials, SUSTAIN 6 (NCT01720446) and PIONEER 6 (NCT02692716), the addition of the glucagon-like peptide-1 analogue semaglutide to standard of care (SoC) in people with T2D at high risk of CVD significantly reduced the risk of major adverse CVD events (3-point MACE: CV death, non-fatal stroke and non-fatal myocardial infarction). Purpose To estimate the effect of adding semaglutide to SoC on CVD-free life-years and 10-year CVD risk in patients with T2D by predicting individual patient-level risk of CVD events in the POOLED cohort using the DIAL CVD risk model. Methods The 3-point MACE hazard ratio from the POOLED cohort (N=6480; HR = 0.76 [95% confidence interval [CI]: 0.62–0.92]) was applied to the patient-level lifetime risk of CVD events derived from the DIAL model. CVD-free life-years and 10-year CVD risk were then calculated based on the age-specific risks of CVD events and non-vascular mortality, using standard actuarial methods. Both new and recurrent CVD events were considered. The DIAL model was validated by comparing the predicted and observed number of CVD events after 1 year. The DIAL model was previously developed using data from people with T2D in the Swedish National Diabetes Registry and validated across geographical regions. Results The DIAL model was considered valid for use in the POOLED cohort because the predicted number of CVD events at 1 year was within 5% of the number observed. Adding semaglutide to SoC was associated with a mean reduction in 10-year CVD risk of 20.0% (95% CI: 6.4–32.6%) and a mean increase of 1.72 (95% CI: 0.52–2.96) CVD-free life-years. The number of mean CVD-free life-years gained ranged from 0.62–2.91 years between age groups (Table). For a 60-year-old male with baseline characteristics matched to the average male from the POOLED cohort, adding semaglutide to SoC reduced 10-year CVD risk by 20.8% and provided 2.53 additional CVD-free life-years. The number of CVD-free life-years decreased when baseline age was increased (Figure). Conclusions The addition of semaglutide to SoC was associated with a gain in CVD-free life-years. This analysis helps contextualize the results of CV outcomes trials and may help to inform clinical decision-making. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novo Nordisk A/S