By Dr. Asnat Raziel, specialist in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal
The SELECT trial: more than weight loss
The SELECT trial changed the way we look at GLP-1 weight-loss injections. The study, published in the NEJM, showed that Wegovy reduces heart attacks, strokes and cardiac death. In other words, Wegovy is not just a weight-loss drug. It is also a treatment that protects the heart.
Following the results, the US Food and Drug Administration (FDA) approved Wegovy in March 2024 for reducing cardiac risk as well. The indication covers adults with cardiovascular disease and with obesity or overweight.
What did the SELECT trial test?
This is one of the largest studies ever run in the field. It enrolled 17,604 people from 41 countries. All of them were aged 45 or older, with overweight or obesity, meaning a BMI (body mass index) of 27 or more. Every participant had established cardiovascular disease, but none of them had diabetes.
Once a week, participants received an injection of semaglutide 2.4 mg, the active ingredient in Wegovy. The comparison group received a placebo. In addition, everyone continued their usual heart treatment. Average follow-up lasted 39.8 months, or more than three years.
The results: fewer heart attacks and strokes
A major cardiac event (cardiac death, heart attack or stroke) occurred in 6.5% of patients on semaglutide. In contrast, such an event occurred in 8.0% of the placebo group. This is a 20% relative reduction in risk.
In absolute numbers, 569 of 8,803 patients on semaglutide had such an event. In the placebo group, 701 of 8,801 had one. Until then, most heart studies of GLP-1 drugs had enrolled people with diabetes. The SELECT trial extended the picture to people with obesity who do not have diabetes.
Weight loss over four years
A further analysis of the trial data looked at the change in weight. After 208 weeks, patients on semaglutide had lost 10.2% of their weight on average, compared with 1.5% on placebo. Waist circumference shrank by 7.7 cm, compared with only 1.3 cm. Moreover, patients kept the weight off throughout all four years.
Does heart protection come only from weight loss?
The answer is complex. An analysis of the SELECT trial in The Lancet examined this question in depth. The researchers found no direct link between the number of kilograms lost and heart protection. On the other hand, a smaller waist circumference was linked to a lower risk of events. By their estimate, only about a third of the benefit came through the drop in waist circumference.
In other words, much of the protection does not depend on weight loss. GLP-1 drugs have several possible mechanisms. They reduce chronic low-grade inflammation and improve blood vessel function. In addition, they help lower blood pressure and improve blood lipids. They also reduce visceral fat, the deep fat around the internal organs. You can read more about these mechanisms in my article on semaglutide and the heart.
Safety and side effects
The treatment has a cost. In SELECT, 16.6% of patients on semaglutide stopped treatment because of side effects, compared with 8.2% on placebo. Most of the effects were digestive: nausea, diarrhea, constipation and vomiting. Therefore, it is important to raise the dose gradually and under medical supervision. For a full review, see my article on the side effects of Wegovy.
What has changed since the SELECT trial?
Since the study came out, new data have accumulated. In the SOUL trial, oral semaglutide reduced cardiac events in people with type 2 diabetes, from 13.8% to 12.0%. In addition, in December 2025 the FDA approved the Wegovy pill for treating obesity. You can read about it in my article on the Wegovy pill for weight loss.
In March 2026, the FDA also approved a higher dose of 7.2 mg for treating obesity. However, SELECT proved the heart protection at the 2.4 mg dose.
Who do the findings apply to?
Precision matters here. The study included only people who already had cardiovascular disease. For example, people who had a heart attack or stroke, or who have peripheral artery disease. Therefore, the heart indication refers to this population. For people with obesity but no heart disease, preventive protection is still under study.
In addition, the drug does not replace usual heart treatment. Participants in the study kept taking drugs to lower cholesterol, to control blood pressure and to prevent clots. That is, Wegovy added protection on top of existing treatment. Lifestyle also remains the foundation: a healthy diet, physical activity, quitting smoking and good sleep.
What the SELECT trial means for patients
The clinical meaning of the SELECT trial is enormous. It strengthens the view that obesity is a chronic disease that requires active treatment. This is just like high blood pressure, diabetes or high cholesterol.
For doctors, this is a shift in thinking. For patients, it is important news: proper treatment of obesity may also lower the risk of heart attack and stroke. Even so, the decision to treat is always made with a doctor, based on each person’s condition.
Bottom line on the SELECT trial
Medicine is in the middle of a change. The SELECT trial showed that Wegovy is not just an injection for weight loss. Ultimately, it is part of the toolbox for preventing heart disease in people with obesity. Moreover, this protection does not come only from the kilograms lost.
This article provides general information and is not personal medical advice. For any question about your treatment, please consult your doctor.
References
Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes
Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial
Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes
FDA Approves Fourth Product Under National Priority Voucher Program, Higher Dose Semaglutide
Novo Nordisk, the maker of the drug, funded the studies.
