Semaglutide and your heart: reading the SELECT trial

Who was in the trial

SELECT enrolled people who already had cardiovascular disease, such as a prior heart attack, stroke or symptomatic artery disease, and who also had overweight or obesity. Half received weekly Wegovy injections and half received placebo, on top of their usual heart care.

This was a secondary prevention trial. In other words, it asked whether semaglutide reduces the chance of another event in people who have already had trouble with their arteries. It was not designed to show whether semaglutide prevents a first event.

What it found

According to the Wegovy prescribing information, the combined outcome of cardiovascular death, nonfatal heart attack or nonfatal stroke occurred in 6.5% of people on Wegovy and 8.0% on placebo over a median of about 41.8 months. That is a hazard ratio of 0.80, or roughly a 20% relative reduction.

Heart attacks showed the clearest drop (3.8% on placebo versus 2.8% on Wegovy). For cardiovascular death and stroke looked at separately, the numbers favored Wegovy but the statistical ranges were wide enough that the trial could not confirm a difference for each one on its own.

• Absolute difference: about 1.5 fewer major events for every 100 people treated over roughly three and a half years.
• The FDA approved this cardiovascular use for Wegovy in adults with established cardiovascular disease and obesity or overweight, alongside diet and physical activity.
• The label now extends the same cardiovascular indication to Wegovy tablets.

What SELECT does not tell you

Because everyone in SELECT already had heart disease, the results do not show that semaglutide prevents a first heart attack in someone with risk factors alone, such as high LDL or ApoB, a family history or a high calcium score. That is a reasonable question, but it is a different one.

The trial also did not replace standard care. Participants stayed on medicines such as statins, blood pressure drugs and antiplatelet therapy. Semaglutide was an addition, not a substitute.

Finally, SELECT tested Wegovy. Compounded semaglutide has not been studied for heart outcomes, is not FDA-approved and has not been reviewed by the FDA for safety, effectiveness or quality. It would be wrong to promise the SELECT result to someone using a compounded product.

Age and safety in the trial

SELECT included many older adults: about 30% were 65 to 75 and 8% were over 75. The label reports no overall difference in effectiveness for people 65 and older. It does note that participants 75 and older on Wegovy had more hip and pelvic fractures than those on placebo, and more serious side effects overall.

The usual semaglutide cautions apply too. The label carries a boxed warning about thyroid C-cell tumors seen in rodents; semaglutide is not used by anyone with a personal or family history of medullary thyroid carcinoma or with MEN 2. Pancreatitis, gallbladder disease, kidney injury from dehydration and stomach side effects are other risks to discuss. It is not for use in pregnancy.

How this shapes your care at HealifyMD

If you have established heart disease and excess weight, the SELECT evidence supports talking about FDA-approved Wegovy specifically, ideally coordinated with your cardiologist or primary care doctor. HealifyMD offers a weight loss membership from $75/month for people using branded GLP-1s obtained through their own coverage.

If you do not have heart disease, your clinician will focus on your measured risk factors, such as blood pressure, lipids, blood sugar and weight-related conditions, and will be clear that SELECT does not directly apply to you. We do not diagnose or manage heart disease; chest pain, breathlessness on exertion or fainting need prompt in-person care.

Relative and absolute numbers

A 20% relative reduction sounds large, and in a trial this size it is meaningful. It helps to see it in absolute terms too: the event rate fell from 8.0% to 6.5% over about three and a half years. Your own benefit depends on your starting risk, which is why clinicians look at your history, blood pressure, lipids and blood sugar rather than quoting a single number.

The benefit was measured over years of continued treatment. Stopping and starting, or using a product that has not been tested, cannot be assumed to give the same result.

Questions to bring to your clinician

• Do I have established cardiovascular disease, and does that make me similar to the SELECT population?
• Which of my heart medicines should continue unchanged if I start a GLP-1?
• Is an FDA-approved product available to me, and would my plan cover it?
• What should I watch for if I am over 75, given the fracture finding?