Real-world SELECT-like obesity cohort shows high MACE risk, semaglutide NNT of 35 to prevent events.
Background
The landmark SELECT trial demonstrated that semaglutide significantly reduced major adverse cardiovascular events (MACE) in individuals with overweight or obesity and established cardiovascular disease (CVD), crucially without diabetes. Despite this, real-world cardiovascular event rates in comparable populations remained uncharacterized. This gap prompted investigation into the actual burden of CVD in such a cohort and the potential impact of semaglutide's known GLP-1R agonism on these real-world outcomes, moving beyond controlled trial settings to inform clinical practice.
Study Design
Researchers utilized healthcare registries and electronic health records from three Swedish regions (2013-2023), covering approximately 40% of the national population. They identified 9652 individuals aged ≥45 years with obesity (body mass index [BMI] ≥30 kg/m2) and established CVD but without diabetes, aligning with the SELECT trial criteria. Cardiovascular outcomes in this SELECT-like obesity cohort were compared with matched individuals from the general population and a broader population with obesity. To estimate the number needed to treat (NNT), the relative treatment effect of semaglutide observed in the SELECT trial was applied to the absolute MACE risks identified in this real-world cohort.
Results
The SELECT-like obesity cohort comprised 9652 individuals with a mean (SD) age of 68.4 (11.3) years and a mean BMI of 33.1 kg/m2 (SD 3.5); 57.9% were men. Most had a history of myocardial infarction (48.1%) or stroke (41.7%). Over a mean (SD) follow-up of 5.4 (3.2) years, MACE occurred in 21.7% of the cohort. This real-world population was older, had a higher proportion of females, and more often had a prior stroke compared to the SELECT trial participants. Applying the estimated effect of semaglutide from the SELECT trial, the NNT to prevent one MACE was 35 (95% CI, 24-66). This suggests a substantial real-world benefit for GLP-1R agonism in this high-risk group.
The real-world MACE rate of 21.7% over 5.4 years in this SELECT-like cohort underscores the high cardiovascular risk in this population, with semaglutide's NNT of 35 highlighting its significant preventive potential.
Key Findings
- A SELECT-like real-world obesity cohort (n=9652) had a mean age of 68.4 years and mean BMI of 33.1 kg/m2.
- MACE occurred in 21.7% of the cohort over a mean follow-up of 5.4 years.
- The real-world cohort was older, had more females, and more prior strokes than the SELECT trial population.
- Applying semaglutide's effect from SELECT, the NNT to prevent one MACE was 35 (95% CI, 24-66).
Why It Matters
This real-world analysis provides crucial validation for the SELECT trial's findings, demonstrating that the high cardiovascular risk observed in the trial cohort is consistent with real-world populations. Semaglutide's cardiovascular benefits are likely generalizable to broader populations with obesity and established CVD without diabetes. The calculated NNT of 35 offers a tangible metric for clinicians and patients, reinforcing the significant impact of GLP-1R agonists in secondary cardiovascular prevention. This insight supports the expanded use of semaglutide in clinical practice for individuals with obesity and CVD, emphasizing its role beyond glycemic control to include robust cardiovascular protection, potentially influencing treatment guidelines and patient management strategies.
semaglutide
obesity
cardiovascular-disease
mace
real-world-data
sweden