Do GLP-1s Have a Cardiovascular Benefit?

The question of whether semaglutide or other GlP-1’s such as Mounjaro, drugs primarily known for their efficacy in treating type 2 diabetes and weight loss, offers cardiovascular benefits to non-diabetic patients has been addressed by a groundbreaking study presented recently. This study, known as the SELECT trial, provides compelling evidence that semaglutide does indeed have significant cardiovascular benefits.

The SELECT trial, the largest ever conducted by Danish pharmaceutical giant Novo Nordisk, is a multicenter, double-blind, randomised, placebo-controlled study. This extensive trial involved over 17,000 participants from 41 countries and spanned five years, from October 2018 to March 2021.

Participants in the trial were 45 years or older, had a Body Mass Index (BMI) of 27 or greater, and had preexisting cardiovascular disease but no history of diabetes. They were randomly assigned to receive either a 2.4mg dose of semaglutide once per week or a placebo*.

The findings of the SELECT trial are significant and indicate that semaglutide can substantially reduce the risk of serious cardiovascular events in non-diabetic patients. Here are the key results:

• Overall Cardiovascular Risk: Patients taking semaglutide experienced a 20% reduction in the overall risk of a cardiovascular event compared to those on the placebo.
• Heart Attack: The risk of a non-fatal heart attack dropped by 28% for those on semaglutide.
• Stroke: There was a 7% reduction in the risk of non-fatal stroke among the semaglutide group.

Beyond cardiovascular outcomes, semaglutide showed several other health benefits:

• Weight Loss: Participants on semaglutide lost an average of 9.39% of their body weight, significantly more than the less than 1% weight loss seen in the placebo group.
• Blood Pressure and Cholesterol: Improvements were noted in blood pressure and cholesterol levels among those taking semaglutide.
• A1C Levels: Although none of the participants had diabetes, semaglutide also improved A1C levels, indicating better blood sugar control.

No. SELECT tested semaglutide 2.4mg, the dose used in Wegovy, so its results belong to that medicine. Mounjaro contains tirzepatide, which acts on two gut hormones, GIP and GLP-1, rather than one. It has its own research programme, and you should not assume the heart findings for semaglutide carry across automatically. If heart health is a big reason you are considering treatment, read how Mounjaro and Wegovy differ and raise it with the clinician reviewing your request.

Having heart disease does not rule you out on its own. SELECT itself enrolled people with established cardiovascular disease. What matters is your full picture. When you complete your consultation, list every diagnosis, any recent heart attack or stroke, and all the medicines you take. A clinician then reviews whether treatment is suitable and safe for you. If something needs checking first, such as a recent change in your heart condition, they may ask you to speak to your GP or specialist.

No. Keep taking any heart, blood pressure or cholesterol medicine exactly as directed. In SELECT, people took semaglutide on top of their usual treatment, not instead of it. As your weight comes down, your blood pressure may fall too. That is welcome, but it can mean your doses need reviewing. If you feel dizzy or light-headed when you stand up, tell your GP rather than changing your tablets yourself.

Probably not entirely. Losing weight eases the strain on your heart, but semaglutide also improved blood pressure, cholesterol and blood sugar in the trial. Later analyses of SELECT suggest the drop in heart events began early, before most people had lost much weight. Researchers think effects on inflammation and blood vessels may play a part, though this is still being studied. The practical point for you is simple: the medicine works best alongside steady habits, not as a replacement for them.

Start with the basics that make the biggest difference. Build meals around lean protein, vegetables, pulses and wholegrains, and keep salt and saturated fat down. Aim for regular movement you can keep up, such as a brisk walk most days. If you smoke, stopping is one of the most effective things you can do for your heart. Keep alcohol within UK low-risk guidance. Our dietary guidelines for weight loss medication users show how to eat well when your appetite is smaller.

Weight regain is common after stopping a GLP-1, and blood pressure, cholesterol and blood sugar can drift back towards where they were before. SELECT followed people while they were taking the medicine, so it does not show how long any heart protection lasts once you stop. If you are thinking about coming off treatment, talk it through with your clinician first. A gradual plan, with your eating and activity habits already in place, gives you the best chance of holding on to your progress.

The SELECT trial's findings highlight the cardiovascular benefits of semaglutide in non-diabetic patients, marking a significant advancement in cardiovascular therapy. As research continues, semaglutide may become a key player in the prevention of cardiovascular events, offering a new avenue for enhancing patient care and health outcomes.

* Placebo is a substance with no therapeutic effect, like a sugar pill, used in research to test if a medicine works by comparing its effects to those who didn't receive the actual medicine.