GLP-1 Medications and Heart Health: Cardiovascular Trial Evidence

Quick Answer

Some GLP-1 medications reduced major cardiovascular events in specific clinical trial populations. In SELECT, Wegovy (semaglutide), a GLP-1 medication given by injection in that trial, reduced the relative risk of the combined cardiovascular endpoint by 20% versus placebo in people with established cardiovascular disease and overweight or obesity, without diabetes.[1] In SURPASS-CVOT, Mounjaro (tirzepatide), a dual GIP/GLP-1 medication, was noninferior, but not superior, to Trulicity (dulaglutide).[3]

The medication, population and comparator matter. Neither a weight-loss percentage nor a lower blood pressure reading is itself proof that a treatment prevents heart attacks or strokes.

Key Points

SELECT and SOUL studied different semaglutide formulations in different patient populations.[1][2]
Wegovy has a US cardiovascular risk-reduction indication for adults with established cardiovascular disease and either overweight or obesity.[8]
Mounjaro's US prescribing information, revised August 2026, includes cardiovascular risk reduction in adults with type 2 diabetes at high risk for these events.[6]
Cardiovascular trial percentages are not a ranking of drugs. SURPASS-CVOT used an active treatment with cardiovascular evidence, rather than placebo.[3]
SUMMIT found fewer cardiovascular-death or worsening-heart-failure events with tirzepatide than placebo in people with obesity-related heart failure with preserved ejection fraction (HFpEF); that is a different question from a MACE trial.[7]
These treatments were added to usual care and were not tested as replacements for prescribed heart medicines.[1][2][3][7]

What the Research Shows

The trials below assessed a combined endpoint involving cardiovascular death, heart attack and stroke, often called major adverse cardiovascular events (MACE). A reduction in the combined endpoint does not mean each component fell by the same percentage.[1][2][3]

Injectable Semaglutide: SELECT (2023)

SELECT enrolled 17,604 adults aged 45 or older with established cardiovascular disease and a body mass index of at least 27, without a history of diabetes. Participants received once-weekly semaglutide with a target dose of 2.4 mg or placebo, alongside standard care.[1]

At a mean follow-up of 39.8 months, cardiovascular death, nonfatal heart attack or nonfatal stroke occurred in 6.5% with semaglutide versus 8.0% with placebo. The hazard ratio was 0.80 (95% confidence interval 0.72–0.90), commonly described as a 20% relative risk reduction.[1]

The difference between the reported event percentages was 1.5 percentage points, not 20 percentage points. Those percentages describe this trial population over its follow-up period, not everyone's personal chance of benefit.[1]

SELECT did not study people with diabetes, and it did not establish prevention of a first cardiovascular event in otherwise low-risk people. It also does not, by itself, prove that the benefit is entirely independent of weight loss.[1]

Wegovy's US label includes reduction of cardiovascular death, nonfatal heart attack and nonfatal stroke in adults with established cardiovascular disease and overweight or obesity, in combination with a reduced-calorie diet and increased physical activity.[8]

Oral Semaglutide: SOUL (2025)

SOUL was published in 2025, not 2024. It enrolled 9,650 adults aged 50 or older with type 2 diabetes and atherosclerotic cardiovascular disease, chronic kidney disease, or both. Participants received oral semaglutide, with a maximum trial dose of 14 mg daily, or placebo in addition to standard care.[2]

During a median follow-up of 49.5 months, MACE occurred in 12.0% versus 13.8%, respectively. The hazard ratio was 0.86 (95% confidence interval 0.77–0.96), corresponding to a 14% relative reduction.[2]

This supports oral semaglutide's cardiovascular efficacy in that population. It does not make different oral products, doses or indications interchangeable, and it is not a newly reported 2026 trial.[2]

The doses above describe the research, not instructions for treatment. Your prescriber determines your actual medication and dose. Do not adjust your dose without consulting them.

Victoza (Liraglutide): LEADER (2016)

LEADER enrolled 9,340 people with type 2 diabetes at high cardiovascular risk. Over a median follow-up of 3.8 years, MACE occurred in 13.0% with liraglutide versus 14.9% with placebo. The hazard ratio was 0.87 (95% confidence interval 0.78–0.97), a 13% relative reduction.[4]

Cardiovascular death was a separate outcome: 4.7% versus 6.0%, with a hazard ratio of 0.78. The 13% figure refers to the combined MACE endpoint, not cardiovascular death alone. LEADER's result should not automatically be assigned to every liraglutide brand or weight-management regimen.[4]

Dulaglutide: REWIND (2019)

The Trulicity cardiovascular trial, REWIND, enrolled 9,901 people aged 50 or older with type 2 diabetes and either previous cardiovascular events or cardiovascular risk factors. Only 31.5% had previous cardiovascular disease, so its population differed from SELECT and SURPASS-CVOT.[5]

Over a median follow-up of 5.4 years, the primary cardiovascular composite occurred in 12.0% with dulaglutide versus 13.4% with placebo. The hazard ratio was 0.88 (95% confidence interval 0.79–0.99), a 12% relative reduction. REWIND included deaths of unknown cause in its cardiovascular-death component.[5]

Tirzepatide: SURPASS-CVOT (2025) and the August 2026 Label

SURPASS-CVOT studied people with type 2 diabetes and established atherosclerotic cardiovascular disease. Unlike the placebo-controlled studies above, it compared tirzepatide with dulaglutide, a treatment already supported by a cardiovascular outcomes trial.[3]

The primary endpoint occurred in 12.2% with tirzepatide versus 13.1% with dulaglutide. The hazard ratio was 0.92 (95.3% confidence interval 0.83–1.01); the trial met its noninferiority criterion but did not establish superiority (P=0.09 for superiority).[3]

Noninferiority means the trial excluded a degree of worsening specified in advance. It does not prove the treatments are identical, nor does the numerically lower event rate establish that tirzepatide is better than dulaglutide at preventing these events.[3]

Mounjaro's US prescribing information, revised August 2026, now includes reducing cardiovascular death, nonfatal heart attack and nonfatal stroke in adults with type 2 diabetes who are at high risk for these events. That label update is distinct from the 2025 trial publication.[6] See our Mounjaro cardiovascular approval article for related coverage; the primary trial and current label are the sources for this summary.

Tirzepatide and Obesity-Related HFpEF: SUMMIT (2024)

SUMMIT asked a different heart-health question. It enrolled 731 people with obesity and heart failure with preserved ejection fraction (HFpEF), regardless of whether they had diabetes, and compared tirzepatide with placebo in addition to usual therapy.[7]

Over a median follow-up of 104 weeks, cardiovascular death or a worsening heart-failure event occurred in 9.9% with tirzepatide versus 15.3% with placebo (hazard ratio 0.62, 95% confidence interval 0.41–0.95). The difference was driven by fewer worsening heart-failure events; cardiovascular deaths were 2.2% versus 1.4%, with a wide confidence interval that did not establish a reduction in cardiovascular death by itself.[7]

SUMMIT also reported a greater improvement in the Kansas City Cardiomyopathy Questionnaire clinical summary score, a measure of heart-failure symptoms and physical limitations. These results apply to the trial's specific obesity-related HFpEF population and should not be treated as proof of benefit for every type of heart failure or as a MACE result.[7]

Retatrutide: Risk Markers Are Not Cardiovascular Outcomes

Lilly's May 21, 2026 TRIUMPH-1 announcement described investigational retatrutide in adults with overweight or obesity without diabetes and reported improvements in weight, systolic blood pressure, lipids and an inflammation marker. It was a sponsor's topline obesity-trial report, not evidence of fewer heart attacks or strokes.[9]

That distinction matters: improving a risk marker is not the same as demonstrating a reduction in clinical events. The announcement described cardiovascular and kidney outcomes as an ongoing area of research.[9]

How GLP-1s May Affect Heart Risk

Trials have documented changes in weight, blood sugar, blood pressure, lipids and inflammation markers alongside treatment. These changes may contribute to cardiovascular effects, but the contribution of each mechanism is not settled. SELECT's primary report describes the mechanisms of cardiovascular protection as still speculative.[1]

For patients, the useful distinction is between measured risk-factor changes and measured clinical events. A blood pressure improvement is worth discussing with your clinician, but it cannot be converted into a personal heart-attack risk reduction using these trial headlines.

What This Means for You

If You Have Type 2 Diabetes

The relevant evidence depends on whether a person's heart and kidney history matches the populations studied and whether the particular medication is approved for that use. The diabetes trials did not all enroll the same risk groups.[2][3][5]

If You Have Overweight or Obesity Without Diabetes

SELECT is directly relevant to people who also have established cardiovascular disease. It does not establish the same heart benefit for someone without that disease.[1]

Cost and Treatment Choice

Coverage, ongoing affordability, tolerability and route of administration can matter alongside cardiovascular evidence. A lower monthly price or a larger weight-loss headline does not establish that a medicine offers the same cardiovascular benefit.

GLP-1s Don't Replace Heart Medications

These trials evaluated treatment alongside usual care, not as a replacement for it.[1][2][3][7] Starting a GLP-1 medicine does not make prescribed blood pressure medicines, statins or aspirin unnecessary. Medication decisions require an individualized review by a qualified clinician.

Frequently Asked Questions

Which GLP-1 medications have cardiovascular outcomes evidence?

Injectable semaglutide in SELECT and oral semaglutide in SOUL reduced major cardiovascular events versus placebo in their studied populations.[1][2] Liraglutide in LEADER and dulaglutide in REWIND also reduced events versus placebo in their studied populations.[4][5] Tirzepatide was noninferior, but not superior, to dulaglutide in SURPASS-CVOT.[3] Brand, formulation and approved population matter; results do not apply automatically to every GLP-1 product.[5][6][8]

Do GLP-1s replace heart medications?

No. These trials evaluated treatment alongside usual care, not as a replacement for it.[1][2][3][7] Starting a GLP-1 medicine does not make prescribed statins, blood pressure medicines or aspirin unnecessary; medication changes belong with your prescriber.

Who was studied in the heart protection trials?

SELECT studied people with cardiovascular disease and overweight or obesity without diabetes.[1] Most other major-event trials discussed here enrolled people with type 2 diabetes and cardiovascular disease, kidney disease or defined cardiovascular risk factors.[2][3][5] SUMMIT separately studied people with obesity-related HFpEF.[7] These findings do not establish the same benefit in healthy, low-risk people.

How quickly do GLP-1s protect the heart?

These trials assessed cardiovascular events over years, not a guaranteed time to protection for an individual.[1][2][5] A change in weight or blood pressure cannot tell you when your personal heart attack or stroke risk has fallen.

This article is for informational purposes only and does not replace medical advice. Always talk to your healthcare provider about cardiovascular risk and medication choices.