Abstract Body (Do not enter title and authors here): Background: Semaglutide reduced the risk of major adverse CV events (MACE) by 20% vs placebo in participants with overweight or obesity and established CV disease (CVD) without diabetes in SELECT. SELECT-LIFE is a non-interventional, survey-based follow-up study of SELECT participants who opted to enroll.
Research Questions: To evaluate long-term post-trial effects of once-weekly semaglutide vs placebo on MACE, obesity-related complications and metabolic-related outcomes.
Methods: SELECT assessed efficacy and safety of once-weekly semaglutide 2.4 mg vs placebo added to standard of care among participants with BMI ≥27 kg/m2 and established CVD without diabetes. SELECT-LIFE is an ongoing, prospective observational study in which participants self-report data via questionnaire every 6 months after SELECT completion, with a planned duration of 10 years. No trial drug was directly provided. We report results from the first three questionnaire cycles completed in November 2024 (median follow-up 16 months). Key endpoints: MACE (all-cause death, non-fatal myocardial infarction, or non-fatal stroke), time to type 2 diabetes (T2D) diagnosis, body weight, cancer incidence, knee replacement surgery, and use of a continuous positive airway pressure (CPAP) device for sleep apnea.
Results: Of 17,604 participants in SELECT, 3435 (19.5%) consented to enroll in SELECT-LIFE; 1760 from the historic SELECT semaglutide arm, and 1675 from the placebo arm. SELECT-LIFE participants were mostly male (76.4%) with a mean age of 64.9 years and body weight of 92.0 kg at study entry. A similar proportion of participants in the historic semaglutide vs placebo arm reported MACE (3.4% vs 3.1%, respectively; Figure 1A) or a new T2D diagnosis (semaglutide: 1.5%; placebo: 1.2%; Figure 1B). Mean (SD) body weight increased from 87.9 kg (17.5) at SELECT-LIFE baseline to 91.4 kg (17.9) in the historic semaglutide arm; and reduced from 96.4 kg (18.6) to 93.5 kg (19.6) in the placebo arm (Figure 2). Numerically fewer participants reported events of cancer, knee replacements, and CPAP device use with historic semaglutide vs placebo (Table 1).
Conclusions: After a median of 16 months post-SELECT completion, there is no additional effect on MACE or progression to T2D after semaglutide study drug discontinuation. However, historic treatment with semaglutide appears to have benefits for knee replacement surgeries and sleep apnea, despite expected partial weight regain.