New research presented at the European Congress on Obesity (ECO25) in Malaga, Spain, reveals that semaglutide, a medication originally designed for type 2 diabetes, can significantly reduce the risk of major heart attacks and other serious cardiovascular events in adults with obesity or overweight who already have heart disease but do not have diabetes.
The findings come from a secondary analysis of the landmark Semaglutide and Cardiovascular Outcomes (SELECT) trial, which showed dramatic benefits as early as three to six months after starting treatment.
Semaglutide belongs to a class of drugs called GLP-1 receptor agonists, which mimic the action of natural incretin hormones in the body. These hormones help lower blood sugar levels after eating, make people feel fuller for longer, and promote weight loss by reducing appetite.
While semaglutide has been widely used for managing diabetes, it is also approved for weight loss in individuals with obesity or overweight who have other health issues.
The SELECT trial, first conducted in 2023, demonstrated that semaglutide could reduce the risk of major heart events—such as heart attacks, strokes, and cardiovascular-related deaths—by 20% over three years in people with obesity but without diabetes.
These participants had previously experienced heart attacks, strokes, or had peripheral artery disease, which put them at high risk for further cardiovascular problems. Notably, the trial did not include any dietary or weight-loss counseling, meaning the benefits were directly linked to the medication itself.
In this new analysis, researchers focused specifically on how quickly semaglutide began to show cardiovascular benefits. They tracked 17,604 adults aged 45 and older from 804 sites in 41 different countries. All participants had a body mass index (BMI) of 27 or higher, classifying them as overweight or obese.
Participants were randomly assigned to receive either weekly injections of semaglutide, gradually increased to a dose of 2.4 mg by week 16, or a placebo.
The results were compelling. Within just three months of starting semaglutide, participants experienced a 38% reduction in major adverse cardiovascular events (MACE)—which include heart attacks and strokes—compared to those on the placebo.
Specifically, 36 participants in the semaglutide group experienced MACE, compared to 58 in the placebo group. This early benefit continued to grow: at six months, semaglutide users saw a 41% reduction in cardiovascular events (67 events versus 113 in the placebo group).
What makes these findings especially interesting is that during these first three to six months, most participants had not yet reached the full target dose of semaglutide (2.4 mg weekly), and many had not lost a significant amount of weight.
This suggests that semaglutide’s cardiovascular benefits are not solely dependent on weight loss, which is traditionally seen as a key factor in improving heart health.
Dr. Jorge Plutzky, Director of Preventive Cardiology at Brigham and Women’s Hospital in Boston and the lead author of the study, emphasized the importance of this early impact: “Our findings reveal an early separation in the treatment effect of semaglutide that occurs even without a significant amount of weight lost and prior to full semaglutide titration.”
Although the exact mechanisms behind semaglutide’s early heart-protective effects are still being studied, Dr. Plutzky suggested several possibilities. These include:
Reduced inflammation: Semaglutide may help lower inflammation levels in blood vessels, which is a major factor in heart disease.
Lowered blood sugar and blood pressure: Even in people without diabetes, semaglutide can improve blood sugar control and reduce blood pressure, both of which reduce strain on the heart.
Direct effects on blood vessels: The drug may have a protective effect on the arteries, making them less prone to blockage.
Early dietary changes: Semaglutide’s appetite-suppressing effects could lead to healthier eating patterns, further lowering cardiovascular risk.
One crucial point the researchers made is that SELECT participants were already taking heart medications, such as those for blood pressure and cholesterol.
This means the benefits of semaglutide were in addition to the protection offered by these other drugs. It shows that semaglutide could be a powerful complementary therapy for people with obesity and cardiovascular disease.
The SELECT trial was not designed to prevent first-time heart attacks or strokes—all participants had a history of cardiovascular disease, placing them at high risk. However, the findings suggest that semaglutide might be a valuable addition to heart disease management, potentially preventing further heart-related events even before significant weight loss is achieved.
These early benefits open up new discussions about how semaglutide might be used for heart protection in high-risk patients, even those without diabetes.
Dr. Plutzky and his team are now looking to explore the underlying biological mechanisms further, hoping to understand exactly how semaglutide reduces heart risks so quickly. If successful, this could lead to more targeted treatments for those at risk of heart disease, providing protection well before traditional weight loss effects take hold.
If you care about heart health, please read studies about top 10 foods for a healthy heart, and how to eat right for heart rhythm disorders.
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