Key result
Obesity with cardiovascular disease is linked to ~2.3-fold higher MACE risk versus the general population.
Why the study?
While semaglutide reduced MACE in the SELECT trial among individuals with overweight or obesity and established CVD without diabetes, real-world cardiovascular event rates in comparable populations remain uncharacterised.
Cohort (n=105,986)
Yes
Individuals matching the SELECT trial criteria in real-world clinical practice carry a high baseline risk of cardiovascular events, indicating a highly favorable potential number needed to treat (NNT=35) for MACE reduction with semaglutide.
High real-world MACE risk in SELECT-like patients supports risk-reduction strategies; extends trial population data but leaves semaglutide effectiveness open.
BACKGROUND: In the SELECT trial, semaglutide reduced major adverse cardiovascular outcomes (MACE) in individuals with overweight or obesity and established cardiovascular disease (CVD) but without diabetes. However, real-world cardiovascular event rates in comparable populations remain uncharacterised. We therefore aimed to (1) assess real-world cardiovascular outcomes in a SELECT-like cohort with obesity, (2) compare them to the general population and a broader population of individuals with obesity and (3) evaluate the cardiovascular preventive potential of semaglutide in this SELECT-like cohort with obesity. METHODS: ) and established CVD but without diabetes, in alignment with the SELECT trial criteria. Cardiovascular outcomes in this SELECT-like obesity cohort were compared with matched individuals from the general population as well as with a broader population of individuals with obesity, irrespective of CVD status or other comorbid conditions. To estimate the number needed to treat (NNT), the relative treatment effect of semaglutide observed in the SELECT trial was applied to the absolute risks identified in the SELECT-like obesity cohort. RESULTS: (SD 3.5) and 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%. Compared with the SELECT trial, this real-world population had a higher mean age, had a higher proportion of females, and more often had a prior stroke. Applying the estimated effect of semaglutide from the SELECT trial, the NNT to prevent one MACE was 35 (95% CI, 24-66). Compared with the General population cohort (n = 48 260), the SELECT-like obesity cohort had a higher burden of cardiovascular and obesity-related comorbidities and an increased risk of adverse cardiovascular outcomes, including MACE (HR 2.3 [2.2-2.4]) and heart failure (HR 2.7 [2.5-2.9]). CONCLUSION: In a real-world setting, despite the use of extensive preventive medications, individuals with obesity and CVD had a higher risk of adverse cardiovascular outcomes and mortality compared with the SELECT trial as well as the general population. These findings highlight the substantial disease burden and the need for improved secondary CVD prevention strategies.
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Ritsinger et al. (2026) conducted a cohort in Obesity and established cardiovascular disease (without diabetes) (n=105,986). Obesity and established cardiovascular disease vs. General population was evaluated on Major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, and stroke) (HR 2.3, 95% CI 2.2-2.4). Compared to the general population, a real-world cohort of individuals with obesity and cardiovascular disease had a significantly higher risk of major adverse cardiovascular events (HR 2.3).
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