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Study Shows Weight Loss Drug Decreases Heart Disease Risk

Contributor Jorge Plutzky, MD
6 minute read
A man prepares to take an injection of weight loss medication

New weight loss drugs have made headlines for their remarkable results. The active ingredient, semaglutide, is available by prescription only. It was initially used to treat type 2 diabetes. Research has shown the medication improves the health of patients with obesity and diabetes.

But what about patients with overweight or obesity who don’t have diabetes? Does the drug still provide a benefit in preventing heart attacks and the need for stents (small mesh tubes that help keep arteries open)? Could the drug help prevent death from heart disease

A recently published study, the SELECT trial (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity), aimed to answer this question. Jorge Plutzky, MD, a Mass General Brigham cardiologist, was instrumental in designing and running the trial as a steering committee member. Dr. Plutzky is director of Preventive Cardiology at Brigham and Women’s Hospital, where he cares for patients and conducts research.

The study showed that patients with overweight or obesity who have a history of heart disease, but no diabetes, had a clear benefit from taking semaglutide. Patients who took the medication had lower rates of significant heart events like heart attack and stroke than patients who received the placebo. According to Dr. Plutzky, this landmark study means that semaglutide could help even more patients in the future.

What is semaglutide?

Semaglutide is a medication that acts like the GLP-1 hormone made by the body after eating. GLP-1 helps the body produce insulin and lower blood sugar levels. It can also affect parts of the brain that control appetite and the feeling of fullness. It’s thought that semaglutide helps reduce appetite by slowing food movement through the body.

Researchers study how semaglutide affects the body to result in weight loss. They also want to study how the drug affects the body in other ways, including the cardiovascular system.

SELECT study of semaglutide to treat patients with overweight or obesity who don’t have diabetes

The SELECT trial took place at 804 clinical sites in 41 different countries, which included a site at the Brigham. The trial was random and double-blinded. This means no one knew which patients took the semaglutide and which took the placebo. 

The study randomized over 17,000 patients, all 45 years or older. They all had a history of heart disease and had overweight or obesity, but none had diabetes. Half received weekly semaglutide injections, while half received the placebo. Patients had treatment for an average of 34 months. They also received follow-up care for an average of 39 months after that.

“The size of the trial, and the fact that it was double blind, defines the most rigorous kind of clinical trials,” Dr. Plutzky says.

A team of investigators designed, oversaw, and then analyzed the results of the study once it was completed. This team included obesity specialists, endocrinologists, statisticians, and cardiologists, including Dr. Plutzky. The trial was then “unblinded,” allowing the investigators to review what happened to the two groups. 

These drugs are not just treatments for diabetes or weight loss. Now we know they are also drugs for treating heart disease.

Jorge Plutzky, MD


Mass General Brigham

Promising results of the SELECT trial

In SELECT, people who received semaglutide had a significant decrease in major heart disease events (heart attacks, strokes, and death) compared to those who got the placebo. As expected with this medication, the patients who took semaglutide also lost significantly more weight. Those on semaglutide also had a greater decrease in blood pressure, triglyceride levels (the amount of fat in the bloodstream), and another marker of inflammation. Inflammation is the body’s response to injury, infection, or certain medical conditions.

The SELECT results, published in the New England Journal of Medicine, have been widely hailed. The results show the potential to transform care for patients with overweight or obesity patients without diabetes who are at high risk of heart disease.

“SELECT was the first study ever to show a definitive cardiovascular benefit associated with losing weight. Earlier weight loss drugs and lifestyle modifications didn’t substantially reduce body weight. They also didn’t improve heart disease outcomes, such as the incidence of heart attacks,” Dr. Plutzky says.

The SELECT trial, and other trials of GLP-1 agonists, have also shown these medications are generally safe. In some people, they can cause stomach-related issues, like nausea. But this often gets better over time or with careful dose changes.

Semaglutide’s success opens up new treatment options. While diabetes increases the risk of heart disease, only 30% of patients with heart disease have diabetes. The SELECT trial shows that heart patients without diabetes who have overweight or obesity could still benefit from taking semaglutide. Thus, the drug could help an even larger population.

“These drugs are not just treatments for diabetes or weight loss. Now we know they are also drugs for treating heart disease,” Dr. Plutzky says.

Additional research to prevent heart disease

As a preventive cardiologist, Dr. Plutzky studies how obesity, diabetes, and heart disease are related. He also plans to do doing more research into how semaglutide affects the body.

“The next stage of research is studying how drugs can be used better and more systematically. For example, we’re analyzing how semaglutide affects changes in inflammation,” says Dr. Plutzky.

Ample evidence, led primarily by work from the Brigham, has shown that chronic, low-grade inflammation can predict future heart risk. Researchers are studying how chronic inflammation affects the heart and coronary artery disease. Building off the success of semaglutide, there are more trials with other agents that target the GLP-1 pathway.

Prescriptions for semaglutide

Patients can get semaglutide by prescription only. There are several forms of GLP-1 drugs that go by different names. Some are approved only for managing type 2 diabetes, while some have shown they can reduce the risk of heart disease. Others are approved for weight loss in patients who qualify.

If you’re interested in trying semaglutide or other medications to manage your weight, diabetes, or risk of heart disease, speak with your primary care provider (PCP) or cardiologist. They can review your current health status and your medical and family history. They can counsel you about potential side effects. They may also recommend lifestyle changes, like exercising more or adjusting your diet. These changes may be helpful for your overall heart health, in addition to semaglutide. 

Jorge Plutzky, MD