GLP-1 Therapy and Cardiovascular Health: What the Research Shows

You’ve probably heard that GLP-1 medications, such as Ozempic® and Wegovy®, might do more than help with weight loss. In fact, recent research reports that they may be good for your heart, too. 

GLP-1 medications were first developed to manage type 2 diabetes, but during large clinical trials, researchers noticed fewer heart attacks, strokes, and cardiovascular deaths among the participants taking them. And this observation opened a major area of GLP-1 research. In this article, we take a closer look at the most important studies, what those findings mean in plain terms, who they may apply to, and what the research still can’t tell us.

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What Are GLP-1 Medications, and How Do They Work?

GLP-1 (glucagon-like peptide-1) is a hormone your body produces naturally. It helps regulate blood sugar, signals fullness to your brain, and slows how quickly your stomach empties. GLP-1 medications, formally called GLP-1 receptor agonists, are designed to mimic this hormone.

The two most widely discussed options are semaglutide (sold as Ozempic® and Wegovy®) and tirzepatide (sold as Mounjaro® and Zepbound®). Their primary approved uses are management of type 2 diabetes and, more recently, chronic weight management in adults who meet certain criteria.

However, these medications are not right for everyone. Eligibility depends on your medical history, goals, and other factors and is determined in consultation with a licensed healthcare provider.

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How GLP-1s Affect the Body Beyond Blood Sugar

GLP-1 receptors aren’t limited to the pancreas. They’re also found in the heart, blood vessels, kidneys, and brain, which is why researchers began investigating possible cardiovascular effects.

In fact, some studies report GLP-1 medications may be associated with reduced inflammation, modestly lower blood pressure, and improved cholesterol levels.

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What the Major Cardiovascular Outcomes Trials Found

A cardiovascular outcomes trial, or CVOT, is a large, long-term study designed to determine whether a medication increases or decreases the risk of serious heart events. After safety concerns around some diabetes drugs in the early 2000s, regulators began requiring these trials. And GLP-1s produced some surprising results.

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LEADER Trial (liraglutide)

The LEADER trial, published in 2016, enrolled around 9,340 people with type 2 diabetes and high cardiovascular risk. Compared with placebo, liraglutide (Victoza®) reduced the risk of major adverse cardiovascular events (MACE), such as heart attack, stroke, and death from cardiovascular causes, by about 13% over a median of 3.8 years. It was the first large trial to demonstrate a clear cardiovascular benefit for a GLP-1 medication, setting the stage for what followed.

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SUSTAIN-6 Trial (semaglutide)

Published the same year, SUSTAIN-6 enrolled about 3,297 people with type 2 diabetes and high cardiovascular risk. Over 104 weeks, semaglutide was associated with a 26% reduction in MACE compared with placebo, driven largely by fewer nonfatal strokes. 

At the same time, it’s worth noting that SUSTAIN-6 was a smaller trial designed to test whether semaglutide was non-inferior to placebo on safety, so this benefit was an exploratory finding.

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SELECT Trial (semaglutide in people without diabetes)

In 2023, SELECT was the first large CVOT to test semaglutide in obese or overweight individuals without type 2 diabetes. It included 17,604 participants aged 45 or older with established cardiovascular disease, including a prior heart attack, stroke, or peripheral artery disease, and a BMI of 27 or higher.

The trial reported that once-weekly semaglutide 2.4 mg (the Wegovy® dose) reduced the risk of MACE by about 20% compared with placebo over about 3.3 years—extending the potential benefit to a much broader group (not solely those with diabetes). But again, every participant already had an established cardiovascular disease, which means these findings can’t be extended to individuals with no cardiac history.

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What These Trials Have In Common (And What They Don’t Tell Us)

Taken together, these trials are encouraging, but they also have limitations, including:

• All enrolled people had type 2 diabetes or established cardiovascular disease, which means the findings don’t automatically apply to someone with no cardiac history or metabolic risk factors.
• Each studied a specific medication at a specific dose; results may not translate directly across all GLP-1 drugs.
• These are population-level averages; individual results vary, and the mechanisms (weight loss, blood pressure, inflammation, and cardiac effects) are still being studied.
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What Happens to Your Heart Health If You Stop GLP-1 Therapy?

A study published in March 2026, in BMJ Medicine, followed more than 333,000 U.S. veterans with type 2 diabetes for up to three years. It reported that stopping or interrupting GLP-1 treatment was associated with a meaningful increase in cardiovascular risk compared with continuous use.

In other words, the risk was duration-dependent. And stopping for two years without resuming was associated with roughly a 22% higher risk of major cardiovascular events versus continuous use; a one-year gap corresponded to about a 14% increase. Even a six-month interruption before restarting appeared to erode the benefit by an estimated 4-8%. By contrast, continuous use over the full three years was associated with an approximately 18% reduction in MACE, equating to about 4 fewer major cardiovascular events per 100 people over that period.

Researchers describe the effect as a kind of “metabolic whiplash.” When people stop GLP-1 therapy, inflammation, blood pressure, and cholesterol may rebound—sometimes before the scale moves much at all. As senior author Dr. Ziyad Al-Aly put it, “Weight regain is visible; the metabolic reversal is not.”

All of the above means that it’s important to discuss these concerns with your provider, particularly if you’re considering stopping GLP-1 therapy due to cost, side effects, or supply issues.

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Why People Stop GLP-1 Therapy (And What That Means for Heart Health)

Individuals may discontinue GLP-1 medications for various valid reasons, including out-of-pocket cost, common GLP-1 side effects (such as nausea or other gastrointestinal discomfort), periodic shortages, and a common but mistaken belief that the benefits are “locked in” after a while. In fact, about half of GLP-1 users stop taking it within the first year.

So, why is this the case? 

For many people, discontinuation is influenced by factors such as cost, access, side effects, and medication availability. However, programs built around ongoing support from healthcare providers, side-effect management, and transparent pricing are designed to remove the common barriers that lead many people to discontinue.

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Do GLP-1 Cardiovascular Benefits Apply to You?

The benefits observed in the major trials were limited to specific groups: individuals with type 2 diabetes and high cardiovascular risk (LEADER, SUSTAIN-6), and individuals with obesity or overweight plus established cardiovascular disease (SELECT). They weren’t studied in individuals with no cardiovascular risk factors or metabolic disease.

This simply means that the cardiovascular evidence is strongest for these profiles:

• Adults with type 2 diabetes and high cardiovascular risk.
• Adults with overweight or obesity (BMI ≥27) and a history of heart attack, stroke, or peripheral artery disease.

GLP-1 therapy may still be appropriate for other individuals for weight management reasons. At the end of the day, a licensed healthcare provider can evaluate whether the overall benefit-and-risk balance makes sense for you.

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The Role of BMI and Obesity in Cardiovascular Risk

Obesity and cardiovascular risk go hand-in-hand. Excess weight contributes to high blood pressure, unhealthy cholesterol, insulin resistance, and chronic, low-grade inflammation, which each raise the risk of a heart attack or stroke. 

Research analyzing GLP-1 cardiovascular and kidney outcomes by BMI category in individuals with type 2 diabetes reported benefits across BMI groups, though the magnitude may vary. In short, addressing obesity medically can be a cardiovascular health intervention in its own right. If you’re curious where you stand, you can check your BMI as a starting point, while keeping in mind it is only one piece of a larger picture.

Beyond the Trials: Proposed Mechanisms for GLP-1 Heart Health Benefits

So, how might these medications protect the heart? Researchers point to several overlapping mechanisms:

• Weight and fat reduction: Reducing visceral (abdominal) fat may ease the metabolic strain excess weight places on the cardiovascular system.
• Blood pressure reduction: GLP-1 medications are consistently associated with modest drops in systolic blood pressure.
• Anti-inflammatory effects: GLP-1 receptors in blood vessel walls may help reduce arterial inflammation, a key driver of the plaque buildup behind atherosclerosis.
• Direct cardiac effects: Since GLP-1 receptors are present in heart muscle itself, these medications may influence heart rate, cardiac output, and resilience to reduced blood flow.

Researchers are still working to understand the relative contribution of each mechanism, and it’s likely that several pathways are supporting these effects.

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What This Means If You’re Considering GLP-1 Therapy

So, how can you use this research wisely? Here are a few things to consider:

• The cardiovascular evidence is growing, but strongest for specific patient profiles; a provider can help you understand whether it applies to you.
• If you’re already on GLP-1 therapy, the discontinuation data suggests staying on it consistently for sustained benefit, with support to manage side effects and cost.
• If you’re considering GLP-1 therapy for weight loss, the cardiovascular data adds another dimension worth discussing with your provider, and the research suggests that ongoing, monitored care may be important when therapy is prescribed. 

This is where a medically supervised GLP-1 therapy program may be considered, depending on what a licensed healthcare provider determines is appropriate for you. 

With Eden, you start with a quick online intake. We then connect you with a licensed provider who reviews your health history, cardiovascular risk factors, and goals to determine whether treatment makes sense. If treatment is prescribed, medication may be dispensed by a licensed pharmacy, and you have access to provider messaging and ongoing check-ins that can help support continuity of care.