Three Details Worth Knowing About the SELECT Study

For some time to come, we will be learning more and more about the details and implications of the landmark SELECT study published yesterday in NEJM and presented at the American Heart Association Scientific Sessions in Philadelphia.

A massive crowd packed the meeting hall yesterday for good reason. These results will change the practice of medicine because they tell us so clearly that obesity care can be both life changing and life saving.

Beyond the headline findings of this landmark study, here are three important details of the SELECT study worth your attention.

1. Mainly White Men

This was a study that enrolled 72% men and 84% White persons. So the study population clearly does not come close to representing the population that suffers from obesity and heart disease. It does, however, reflect some of the disparities in cardiovascular and obesity care. With elegant understatement, Amit Khera and Tiffany Powell-Wiley pointed this out in the editorial that accompanied the study:

“Given the underrepresentation of Black, Asian, and Hispanic or Latino populations and of women in the SELECT trial, future trials should be adequately powered to examine the effectiveness of these therapies according to race, ethnic group, and sex.”

Nonetheless, we note that outcomes for the primary endpoint of cardiovascular deaths, strokes, and heart attacks were similar across all prespecified subgroups, which includes sex, race, and ethnicity.

2. More Than Weight Loss

While the public focuses on weight loss, those who pay attention know the benefits of obesity care come from more than just weight loss. Indeed, the cardiovascular benefits of therapy showed up in this trial more quickly than weight changes did. This reminds us once again that focusing on cardiometabolic health more broadly in obesity care is important.

3. Cardiovascular and All-Cause Mortality

The primary endpoint for this study was a composite of cardiovascular deaths, strokes, and heart attacks. Semaglutide therapy yielded a significant 20% reduction in these. But for cardiovascular deaths alone, the reduction was 15% and it fell short of statistical significance. The advantage for deaths from all causes appeared to be greater, but the statistical design of the study precludes any firm conclusions.

Christie Ballantyne, Director of the Cardiometabolic Disease Prevention Center at the Baylor College of Medicine, commented on this for Medscape:

“Adjudication of dead or alive is something that everyone gets right. In contrast, the cause of death is sometime difficult to ascertain. Most importantly, the benefit on total mortality also provides assurance that this therapy does not have some adverse effect on increasing noncardiovascular deaths.”

More to Come

This was a massive landmark study. More details and insights will surely spill forth from the rich trove of data it produced. We will also see more cardiovascular outcome studies for other advanced obesity therapies. These are indeed exciting times for progress in obesity care.

Click here and here for the study and editorial that goes with it. For a detailed discussion of the study, this reporting from Medscape is well worth your time.

Detail of a Buddhist Temple Doorknob, photograph by AngMoKio, licensed under CC BY-SA 3.0

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November 12, 2023