Wegovy and Heart Health: What the SELECT Trial Found

The SELECT trial showed that semaglutide 2.4mg, the medicine in Wegovy, reduced the risk of heart attack, stroke and cardiovascular death by 20% compared with placebo in adults who already had cardiovascular disease and were overweight or living with obesity, but did not have diabetes. It was the first large trial to show that a weight-management medicine reduces major cardiovascular events. On the strength of SELECT, the MHRA extended the Wegovy licence in 2024, and in May 2026 NICE recommended semaglutide on the NHS for this purpose in TA1152. This guide explains what SELECT did and did not show, and what it means for you.

Why a heart outcomes trial mattered

Obesity is strongly linked to cardiovascular disease, including heart attacks, strokes and heart failure. Weight loss improves many risk factors, such as blood pressure, cholesterol and blood glucose. But for decades, no weight-loss medicine had been shown to reduce the actual events that matter: heart attacks, strokes and deaths. Some older weight-loss drugs had been withdrawn because of cardiovascular safety concerns.

That is why regulators and clinicians distinguish between surrogate markers (things like blood pressure or cholesterol that are associated with risk) and hard outcomes (events that patients experience). A medicine can improve surrogate markers without reducing events. SELECT was designed to test hard outcomes directly.

Semaglutide already had cardiovascular outcome data in people with type 2 diabetes. In SUSTAIN-6 (NEJM, 2016), once-weekly semaglutide (the medicine in Ozempic, at diabetes doses) reduced major cardiovascular events compared with placebo in people with type 2 diabetes at high cardiovascular risk. SELECT asked whether that applied to people without diabetes, at the higher 2.4mg dose used for weight management.

How SELECT was designed

SELECT was a large, randomised, double-blind, placebo-controlled trial, published in the New England Journal of Medicine in November 2023.

Who took part

Most participants qualified because of a previous heart attack. Most were already taking standard cardiovascular treatments, including statins and antiplatelet medicines, and many were taking blood pressure medicines.

What they received

Participants were randomly assigned to once-weekly semaglutide, stepped up to 2.4mg, or matching placebo injections. Both groups continued standard care for their heart disease. Unlike the STEP weight-loss trials, SELECT did not include an intensive lifestyle programme.

What was measured

The primary outcome was a composite of major adverse cardiovascular events (MACE):

• death from cardiovascular causes
• non-fatal heart attack (myocardial infarction)
• non-fatal stroke

Participants were followed for an average of 39.8 months, just over three years.

What SELECT found

The main result

Source: Lincoff and colleagues, NEJM 2023. Because of the trial's hierarchical testing plan, the result for cardiovascular death was not statistically significant, so the secondary outcomes below it (including death from any cause) are considered supportive rather than confirmed.

Putting 20% into context

A hazard ratio of 0.80 means a 20% relative reduction in the rate of major cardiovascular events. In absolute terms, the difference in the proportion of people who had an event over about three years was 1.5 percentage points (8.0% vs 6.5%). Put another way, roughly 67 people would need to be treated for about three years to prevent one major cardiovascular event, based on the trial averages.

Both figures matter. Relative reductions show how strongly a treatment works; absolute differences show how many people benefit over a given time. For comparison, many established heart treatments produce relative risk reductions of a similar order. Your own absolute benefit depends on your baseline risk: people at higher risk tend to gain more.

Weight loss in SELECT

Average weight loss was about 9.4% at two years with semaglutide, smaller than in the STEP trials. This is likely because SELECT participants were older, mostly men, had established heart disease, and did not receive an intensive lifestyle programme. A later analysis in Nature Medicine (2024) reported that weight loss was sustained to four years, at around 10% on average, for people who stayed on treatment.

Is the heart benefit just about weight loss?

This is one of the most interesting questions SELECT raised. Several observations suggest weight loss is not the whole story:

• Timing. The curves for cardiovascular events began to separate early in the trial, before most weight had been lost.
• Weight independence. A pre-specified analysis published in The Lancet (2024) found that the cardiovascular benefit was broadly similar regardless of participants' starting BMI or waist size, and regardless of how much weight they went on to lose.
• Risk factors. Semaglutide improved blood pressure, blood fats and markers of inflammation (such as C-reactive protein), but the size of these changes does not fully explain the reduction in events.

Researchers think semaglutide may act through several pathways, including direct effects on blood vessels and inflammation, as well as weight and risk-factor changes. The exact mechanisms are still being studied. The practical point is that people in SELECT who lost relatively little weight still appeared to benefit. Our guide to how Wegovy works covers the biology of GLP-1 receptors.

Side effects and safety in SELECT

SELECT also provides useful long-term safety information because of its size and duration.

• Stopping because of side effects: 16.6% of people on semaglutide stopped the medicine because of adverse events, compared with 8.2% on placebo. Gastrointestinal effects such as nausea, vomiting and diarrhoea were the main reason.
• Serious adverse events: these were reported less often with semaglutide (about 33% vs 36%), partly reflecting fewer cardiovascular events.
• Gallbladder problems: gallbladder-related disorders were somewhat more common with semaglutide, consistent with other GLP-1 trials and with rapid weight loss in general.
• Pancreatitis: acute pancreatitis was rare and not significantly different between groups in SELECT, though it remains a recognised risk in the SmPC.

Our Wegovy side effects guide explains how common and serious side effects are managed.

What SELECT did not show

Being clear about the limits of a trial is as important as reporting its headline result.

• It did not include people without established cardiovascular disease. SELECT does not show whether semaglutide prevents a first heart attack or stroke in people at risk but without existing disease.
• It did not include people with type 2 diabetes. That group was studied separately in SUSTAIN-6 and other trials.
• It was mostly men. Around 28% of participants were women, so estimates for women are less precise, though pre-specified subgroup analyses did not show clear differences.
• It does not tell us what happens after stopping. There is no evidence that the benefit persists once semaglutide is stopped. See our Wegovy maintenance guide.
• It was funded by the manufacturer. Like most large drug trials, SELECT was sponsored by Novo Nordisk. It was independently peer-reviewed and published in a leading journal, and the results were assessed by regulators and by NICE.

UK licensing and NICE guidance

The licence

Following SELECT, the MHRA extended the Wegovy licence in 2024 to include reducing the risk of major adverse cardiovascular events in adults with established cardiovascular disease and either obesity or overweight (BMI of 27 or more), alongside a reduced-calorie diet and increased physical activity. The current SmPC on medicines.org.uk contains the exact wording.

The higher 7.2mg dose authorised in January 2026 does not apply to people using Wegovy solely to reduce cardiovascular risk.

NICE TA1152

In May 2026 NICE published TA1152, recommending semaglutide (up to a maintenance dose of 2.4mg once weekly), alongside a reduced-calorie diet and increased physical activity, as an option for reducing the risk of major adverse cardiovascular events in adults with established cardiovascular disease and a BMI of at least 27. NICE estimated that more than a million people in England could be eligible.

The guidance does not specify where semaglutide should be prescribed, so integrated care boards decide how it is delivered locally. Commissioners in England are normally expected to fund NICE-recommended treatments within 90 days, but practical access may take longer in some areas. This is separate from the weight-management guidance, NICE TA875, which recommends semaglutide within specialist weight management services for up to two years. Our guide to Wegovy on the NHS explains how the two recommendations differ.

How SELECT compares with other evidence

Tirzepatide (Mounjaro) produced greater average weight loss than semaglutide in the head-to-head SURMOUNT-5 trial, but weight loss and cardiovascular outcomes are different questions. If cardiovascular protection is a key goal for you, ask your prescriber which medicine has the strongest outcome evidence for someone in your situation. Our Mounjaro vs Wegovy comparison sets out the wider differences.

How to read the numbers: a short primer

Trial results can be confusing, so here is a brief guide to the terms used above.

• Composite outcome. MACE combines several events into one measure. Composites make trials more efficient, but the individual parts may not all move equally. In SELECT, non-fatal heart attacks showed the clearest reduction, while the reduction in cardiovascular death on its own did not reach statistical significance.
• Hazard ratio. A hazard ratio compares the rate of events over time in two groups. A value of 0.80 means events happened at about 80% of the rate in the semaglutide group compared with placebo.
• 95% confidence interval. This is the range within which the true effect is likely to lie. For the primary outcome it ran from 0.72 to 0.90, which does not cross 1.0, so the result is statistically significant. For cardiovascular death it ran from 0.71 to 1.01, which just crosses 1.0.
• Hierarchical testing. To avoid finding chance results by testing many outcomes, SELECT tested secondary outcomes in a fixed order. Once one outcome was not significant, the ones below it could not be formally confirmed, even if their numbers looked favourable.
• Absolute vs relative risk. A 20% relative reduction sounds large, and it is meaningful, but the absolute difference over about three years was 1.5 percentage points. Both are true, and both matter.

Understanding these terms helps you interpret headlines about SELECT, which sometimes overstate or understate what it found.

Other findings from SELECT

Because SELECT was so large and long, researchers have published a series of further analyses. These are secondary or exploratory, so they should be read as supporting rather than definitive evidence. Areas studied include:

• Kidney outcomes, where analyses suggested a slower decline in kidney function with semaglutide.
• Heart failure, where the heart failure composite outcome favoured semaglutide.
• Weight and body shape over four years, showing sustained reductions in weight and waist size in people who stayed on treatment.
• Prediabetes, where fewer people on semaglutide progressed to type 2 diabetes during the trial.

None of these analyses changes the main message, but together they suggest semaglutide's effects reach beyond the scales. They also highlight that benefits were measured while people were taking the medicine.

Questions to ask your GP or cardiologist

If you have established cardiovascular disease and are considering semaglutide, these questions can help focus the conversation:

• Do I meet the criteria in NICE TA1152, and how is it being provided in this area?
• How much might semaglutide reduce my personal risk, given my other treatments?
• Are there any reasons it might not be suitable for me, such as kidney function, gallbladder history or other medicines?
• How will my other heart medicines be monitored if my weight and blood pressure fall?
• What should I do if side effects make it hard to eat, drink or take my other tablets?
• How long would I be expected to take it, and what happens if I stop?

What SELECT means if you have heart disease

If you have had a heart attack, stroke or symptomatic peripheral arterial disease and have a BMI of 27 or more:

• Semaglutide may be an option under the licence and NICE TA1152. Ask your GP or cardiology team whether it is suitable and how it is provided locally.
• It is an addition, not a replacement. Keep taking statins, antiplatelets, blood pressure medicines and any other treatments your doctor has prescribed.
• Lifestyle still matters. Stopping smoking, regular physical activity, cardiac rehabilitation and a heart-healthy diet remain central to secondary prevention.
• Side effects need managing. Gastrointestinal effects are common during dose escalation. If they are severe, your prescriber may slow the step-up or pause at a lower dose.
• Other conditions matter. Your doctor will consider kidney function, any history of pancreatitis or gallbladder disease, and other medicines before prescribing.

If you do not have established cardiovascular disease but are interested in Wegovy for weight management, the relevant evidence is the STEP programme (see our Wegovy results guide) rather than SELECT.

Private prescribing and heart health

Some people with cardiovascular disease consider private prescribing. If you do, it is particularly important that the prescriber has your full medical history, including details of your heart condition and current medicines, and that your GP and cardiology team are informed. A regulated online service should ask about cardiovascular history and may ask for consent to share information with your GP. Our provider comparison sets out how services handle medical history and GP communication, and our prices page explains what affects private costs.

When to speak to a professional

Speak to your GP, cardiologist or prescriber if:

• You have established cardiovascular disease and want to know whether semaglutide is suitable for you.
• You are taking Wegovy and are considering stopping it, especially if you have heart disease.
• You notice your blood pressure dropping, feel light-headed or faint, or your heart rate seems fast at rest.
• You have heart failure and notice increasing breathlessness or ankle swelling.

Call 999 immediately if you have symptoms of a heart attack or stroke:

• Chest pain, pressure or tightness, which may spread to your arms, neck, jaw or back, especially with sweating, breathlessness or nausea.
• Face drooping on one side, arm weakness, or slurred speech (remember FAST: Face, Arms, Speech, Time to call 999).

Seek urgent medical help (NHS 111, or 999 in an emergency) if you are taking Wegovy and develop:

• Severe, persistent abdominal pain, sometimes spreading to the back (possible pancreatitis).
• Persistent vomiting or diarrhoea with signs of dehydration, which can also affect kidney function.
• Upper right abdominal pain with fever or yellowing of the skin or eyes.
• Sudden loss of vision or blurred vision in one eye.

For more on semaglutide injections, visit our Wegovy hub. Whether semaglutide is appropriate for you is a decision for a prescriber who knows your full medical history.