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Semaglutide cuts heart risk — but we don't fully know why. A new analysis of the SELECT trial found that semaglutide reduced major cardiovascular events by 20% in people with obesity and heart disease, but improvements in weight, blood pressure, and other risk factors only partially explain the benefit. Something else appears to be at play.
Semaglutide is already known to cut the risk of major adverse cardiovascular events (MACE) by 20% in people with obesity and established heart disease — but a new analysis published in the European Heart Journal reveals that the "why" is still largely a mystery. Researchers dug into the SELECT trial data to figure out how much of that cardiovascular benefit could be explained by improvements in known risk factors like weight, waist circumference, blood pressure, and inflammation markers.
The short answer: not much. Even when combining eight key risk factors, they only accounted for about 31% of semaglutide's cardiovascular benefit — leaving the majority of the effect unexplained. This suggests the drug may have additional, as-yet-unknown mechanisms protecting the heart.
By the Numbers:
Why it matters: These findings challenge the assumption that semaglutide's heart benefits are simply a byproduct of weight loss. For clinicians, this raises important questions about the drug's full mechanism of action — and could eventually support its use in broader cardiovascular risk reduction strategies beyond obesity management.
