Getting to the heart of GLP-1

With the use of GLP-1 medications on the rise, cardiologists are seeing benefits to heart health, and it might not all be related to weight loss alone.

GLP-1 medications, including semaglutide, are a class of drugs that act on receptors throughout the body, influencing insulin sensitivity, appetite regulation, inflammation and metabolic health. These therapies traditionally were used to treat diabetes; however, weight loss is a well-recognized side effect, and they are now used for weight loss goals. 

“It is known that maintaining a healthy weight is an important part of heart health. GLP-1 receptor agonists can help with achieving a healthy weight, which can be beneficial to the heart,” said Dr. Layla Abushamat, assistant professor of medicine at Baylor College of Medicine. “However, now there is emerging research that is looking into the heart-protective benefits of the drug itself, beyond weight loss.”

Weight loss and heart health

The American Heart Association now recognizes excess and dysfunctional adipose (fat) tissue as one of the key drivers of cardiovascular disease.

“Adipose tissue is not passive; it functions as an endocrine organ, releasing hormones that communicate with the body, including the cardiovascular system,” Abushamat said.

Excess adipose tissue is associated with chronic, low-grade inflammation, insulin resistance, abnormal cholesterol levels, high blood pressure and metabolic syndrome, all of which are associated with increased risk of heart disease and stroke.

GLP-1 therapies can benefit all of these factors, helping with weight loss, improving blood sugar control, lowering blood pressure, improving cholesterol profiles and reducing inflammation all at the same time.

Beyond the scale

“There is a pivotal study called the SELECT Trial, published in 2023, that showed reduction in cardiovascular events in people with overweight or obesity and cardiovascular disease who took semaglutide,” Abushamat said.

The study enrolled adults with overweight or obesity and cardiovascular disease. Participants treated with semaglutide experienced a 20% reduction in major cardiovascular events.

Further analysis looked at whether a greater weight loss led to even more benefits, but results showed that the benefits were seen regardless of starting weight or how much weight participants lost.

“This potentially suggests that mechanisms beyond weight loss, such as reduction in inflammation or direct effects on the heart and blood vessels, may play a role,” Abushamat said.

Is it safe?

GLP-1 therapies are not magic pills. As with any type of medication, there are side effects and they should be taken under the direction of a healthcare provider.

Some side effects include gastrointestinal issues, dehydration, electrolyte abnormalities, loss of muscle mass and cardiovascular effects such as increased heart rate. Certain conditions, such as a personal or family history of medullary thyroid cancer or pregnancy, are contraindicated and those with unexplained pancreatitis or history of severe gastrointestinal diseases require special caution.

“These are all factors that should be discussed with a doctor to find out if you are the right candidate for this type of medication,” Abushamat said.

The body naturally produces GLP-1 in response to eating, but it functions differently from pharmaceutical versions of GLP-1 therapies.

“Online prescriptions or products that claim to naturally produce GLP-1 are not the same as the pharmaceutical versions. Those also often do not include proper evaluations or follow-up visits with a doctor. These are not FDA-approved products and could pose significant risks,” Abushamat said.

Claims of “natural GLP-1 boosters” are unsupported by scientific evidence.

“We do know that once you stop a GLP-1, there is a risk of weight regain. From the clinical trials, those who stopped these therapies regain around two-thirds of the weight that was lost, so focusing on weight loss maintenance is also important,” Abushamat said. “This is another reason why talking to your healthcare provider and being monitored by a healthcare provider when using this type of therapy is so important to overall reduction of cardiovascular illness.”