Some GLP-1 medicines have lowered the rate of heart attack, stroke and cardiovascular death in large randomized trials. The benefit was shown in two groups: people with type 2 diabetes at high cardiovascular risk, and people with overweight or obesity who already had cardiovascular disease.
That is narrower than the headlines suggest. No large outcome trial has shown that these medicines prevent a first heart attack in people who have neither diabetes nor existing heart disease. This guide explains what was tested, in whom, and what is still unknown. It is not a recommendation.
Key takeaways
- GLP-1 medicines were built for type 2 diabetes, and their heart evidence started there.
- In the SELECT trial, semaglutide lowered major cardiovascular events by about a fifth in people with obesity and existing heart disease but no diabetes.
- The heart benefit in SELECT did not track closely with how much weight people lost.
- Trial participants were already at high risk, so the results do not automatically apply to lower-risk adults.
- These medicines were added to standard care in trials and were not tested as replacements for it.
What GLP-1 medicines are
GLP-1 is a gut hormone released after eating. It prompts insulin release, slows stomach emptying and reduces appetite. GLP-1 receptor agonists are medicines that copy it. Liraglutide, dulaglutide and semaglutide are examples. Tirzepatide acts on the GLP-1 receptor and on a second hormone receptor called GIP.
They were developed to lower blood sugar in type 2 diabetes. Their first large heart trials were designed mainly to check cardiovascular safety in people with diabetes, and that is where the benefit first appeared.
What the diabetes trials showed
The LEADER trial followed 9,340 people with type 2 diabetes and high cardiovascular risk for a median of 3.8 years. Cardiovascular death, heart attack or stroke occurred in 13.0% of the liraglutide group and 14.9% of the placebo group.1 Death from cardiovascular causes was also lower.
Later trials tested other medicines in the class. A meta-analysis of eight trials with 60,080 people with type 2 diabetes found that GLP-1 receptor agonists reduced major cardiovascular events by 14% and death from any cause by 12%.2 Hospital admission for heart failure fell by 11%.
The evidence now extends to a tablet. In the SOUL trial of 9,650 people with type 2 diabetes plus artery disease, kidney disease or both, major cardiovascular events occurred in 12.0% of those taking oral semaglutide and 13.8% of those taking placebo.3
Tirzepatide has one large cardiovascular trial so far, and it had no placebo group. SURPASS-CVOT compared it with dulaglutide, a GLP-1 medicine already shown to reduce events, in more than 13,000 people with type 2 diabetes and artery disease.
A major cardiovascular event occurred in 12.2% of the tirzepatide group and 13.1% of the dulaglutide group.4 That met the test for being no worse than dulaglutide. It did not meet the statistical test for being better.
How diabetes itself raises risk is covered in diabetes and heart disease risk.
SELECT: the trial in people without diabetes
SELECT asked whether the heart benefit holds without diabetes. It enrolled 17,604 adults aged 45 or older who had a body-mass index of 27 or higher and existing cardiovascular disease, and who had no history of diabetes.
After a mean follow-up of about 40 months, cardiovascular death, heart attack or stroke had occurred in 6.5% of the semaglutide group and 8.0% of the placebo group.5 That is a relative reduction of 20% and an absolute difference of 1.5 percentage points.
Side effects mattered. Adverse events led 16.6% of the semaglutide group to stop the trial medicine for good, compared with 8.2% of the placebo group. In this class, stomach and bowel symptoms are the most common reason people stop.
| Trial | Who was studied | Main heart result |
|---|---|---|
| LEADER (liraglutide) | Type 2 diabetes, high cardiovascular risk | 13.0% vs. 14.9% with placebo |
| SOUL (oral semaglutide) | Type 2 diabetes with artery or kidney disease | 12.0% vs. 13.8% with placebo |
| SELECT (semaglutide) | Overweight or obesity with existing cardiovascular disease, no diabetes | 6.5% vs. 8.0% with placebo |
| SURPASS-CVOT (tirzepatide) | Type 2 diabetes with artery disease | 12.2% vs. 13.1% with dulaglutide |
Is the benefit just weight loss?
It does not appear to be. A planned analysis of SELECT found that the benefit was consistent across all starting weights and waist sizes. Among people taking semaglutide, the amount of weight lost by week 20 showed no linear link to later cardiovascular events.
Waist size told a little more. The authors estimated that about a third of the observed benefit was explained by a smaller waist.6 They concluded that some of the protection works through routes other than fat loss. What those routes are is not settled.
This matters for how you read your own results. Losing weight on one of these medicines is not proof of heart protection, and losing little is not proof of none. See weight loss and heart risk for the wider picture.
Limits of the evidence
- High-risk participants. Every trial above enrolled people with diabetes, existing cardiovascular disease or both.
- No trial in low-risk adults. Whether these medicines prevent a first event in people without diabetes or known disease has not been shown.
- Results belong to each medicine. Trials tested specific medicines and strengths. A result for one does not prove the same for another.
- Added, not swapped. The diabetes trials gave the medicine on top of standard care, not in place of it.
- Time frame. The placebo-controlled trials ran about three to four years.
GLP-1 medicines are not cholesterol medicines, and the trials did not test them as a substitute for one.
Do not start, stop or change the dose of a GLP-1 medicine, or any other medication, without talking with your prescriber. That applies to products bought online as well.
Next step: measure the risk these medicines act on
GLP-1 trials enrolled people by their risk, so the useful first question is what yours is. Both Cardio Res-Q assessments, the Comprehensive Assessment ($775) and the Enhanced Assessment ($999), measure insulin, glucose and A1c along with ApoB, Lp(a) and hs-CRP. Our insulin resistance page explains the metabolic markers.
See the Cardio Res-Q program page for details, and what you leave with for how results are explained. For questions about which medications the clinic prescribes, ask our team.
Are You a Candidate for Cardio Res-Q?
Three quick questions about the risk factors we screen for. Your answers stay between you and the clinic.
Frequently asked questions
Do GLP-1 medicines prevent heart attacks?
In people with type 2 diabetes at high risk, and in people with overweight or obesity who already had cardiovascular disease, specific GLP-1 medicines reduced a combined measure of cardiovascular death, heart attack and stroke. The absolute reductions were about 1.5 to 2 percentage points over three to four years. There is no comparable trial in people at low risk.
I do not have diabetes or heart disease. Does SELECT apply to me?
Not directly. Everyone in SELECT already had cardiovascular disease. The trial does not show what happens in people without it. That is a question to raise with your clinician, who can look at your overall risk.
Can a GLP-1 medicine replace my statin or blood pressure medication?
The trials did not test that. In the diabetes trials the GLP-1 medicine was added to standard care. Any change to what you take should come from your prescriber.
Related reading
This article is for general education and is not medical advice. Decisions about testing and medication should be made with your clinician. If you have chest pain or other symptoms of a heart attack, call 911.
