The Heart Benefit Is Real. Women Were a Third of the Room.

The claim, first

This is not a marketing line. Wegovy's label carries an FDA indication to reduce the risk of major adverse cardiovascular events — cardiovascular death, non-fatal heart attack, non-fatal stroke — in adults with established cardiovascular disease and either obesity or overweight¹. An indication is a regulatory finding, not a press release.

Behind it sits SELECT, published in the New England Journal of Medicine in 2023. It enrolled 17,604 people aged 45 or older who had pre-existing cardiovascular disease, a BMI of 27 or above, and no diabetes. Half received weekly semaglutide 2.4 mg, half placebo, and they were followed for a mean of 39.8 months².

The primary endpoint occurred in 6.5% on semaglutide against 8.0% on placebo — a hazard ratio of 0.80, or roughly a 20% reduction, with a p-value below 0.001². For a drug most people think of as a weight-loss product, that is a serious cardiovascular result.

It is also not the whole page. Two things sit alongside it that rarely travel with the headline.

The number that got left behind

Sixteen point six percent of people in the semaglutide group stopped the trial drug permanently because of adverse events, against 8.2% on placebo².

One in six. That is the same trial, the same table, and it is the figure that decides whether a benefit measured over three years is available to you at all. A 20% risk reduction assumes you are still taking it.

Who was actually in these trials

Here is where this gets specific to the person reading it.

A 2024 systematic review in the International Journal of Stroke pooled the cardiovascular outcome trials for this whole drug class — 11 trials, 82,140 participants, a cumulative 247,596 person-years of follow-up. Stroke was less common on GLP-1 drugs than placebo: a relative risk of 0.85, with a number needed to treat of 200³.

Of those 82,140 participants, 34.6% were women³.

Sit with that for a second. The cardiovascular case for this entire class of drugs — the case now printed on a label, the case a cardiologist will cite to you — was built on a population that was roughly two-thirds men.

That is not unusual in cardiovascular medicine, which is part of why it is worth saying out loud. Women have been under-enrolled in cardiac trials for decades, and the consequence is not that findings are wrong. It is that they are less precisely measured in us, and that questions specific to us go unasked.

Participants in these trials were also older and sicker than most people who now take these drugs. SELECT required an existing cardiovascular diagnosis and a minimum age of 45, and excluded anyone with diabetes². Women in the study were, by design, women who had already had a cardiac event or diagnosis — not women taking a GLP-1 in their thirties or forties to lose weight. That gap between who was studied and who is prescribed is the real limitation here, and it is larger than the sex imbalance.

What this does not mean

It does not mean the benefit skips women, and this is the part I want to be careful about, because it would be an easy and irresponsible place to land.

A 2025 review in Current Psychiatry Reports looked directly at sex differences in obesity and its treatment. Its finding on this point is reassuring: among the small number of studies that analyzed changes in obesity-related conditions stratified by sex, improvements in heart failure and cardiovascular outcomes were consistent between males and females⁴.

So the honest reading is narrower than a headline in either direction. The benefit appears to hold for women. It was established on a population where women were a minority, and the sex-stratified analyses that exist are few. Under-representation is a reason to ask what was measured in women — not a reason to discount a finding this size.

Two things that do differ

The same review reports two sex differences that are more immediately useful than the trial demographics, and they run in opposite directions⁴.

The first row is the one that quietly shapes how women get treated: for decades, diet-and-exercise advice produced smaller average results in women, and that gap was frequently read as a failure of effort. The second row inverts it. On these medications, women lost more weight on average than men.

The third row is the cost. Women reported more adverse events — the nausea and vomiting that make up most of the discontinuation figure above. More benefit and more side effects, in the same population.

That combination is worth naming before you start, because it means the odds of it working well for you and the odds of it being unpleasant are both a little higher than the average trial figure suggests.

What to ask

If a clinician offers you one of these for cardiac reasons rather than weight, the useful questions are specific.

"Am I the population in the trial?" SELECT enrolled people with established cardiovascular disease and no diabetes². If you have neither an existing cardiac diagnosis nor diabetes, the 20% figure is not describing you, and nobody has run your trial.

"What is the plan when the nausea arrives?" Given the 16.6% discontinuation rate² and the finding that women report more adverse events⁴, a titration plan is not a detail — it is the difference between getting the benefit and stopping.

"Is this in place of, or alongside, the rest?" Nothing in SELECT compared semaglutide against statins, blood pressure control or smoking cessation. It was tested on top of usual care.

The bottom line

A 20% reduction in major cardiac events is a genuine finding and it is now regulatory fact. It was demonstrated in 17,604 people over more than three years, and the class-wide stroke signal points the same way across 82,140 participants.

It was also demonstrated in a room that was about a third women, at a cost of one in six stopping for side effects — and the best available evidence says the benefit holds for us anyway, on fewer analyses than any of us would like.