Keywords: diabetes, weight loss, obesity, semaglutide, Ozempic, Wegovy, Rybelsus

This article was originally published in the Northwestern University Feinberg School of Medicine News Center. It has been edited for the HealthBeat audience.

Semaglutide, a medication sold under the brand names Ozempic®, Wegovy® and Rybelsus®, has shown to be effective at helping patients lose weight. Now, studies indicate it may also reduce the risk of cardiovascular disease.

What the Studies Say

“It’s likely due to weight loss and the drug itself having what we call ‘weight-independent effects’ on cardiovascular events — things like reduced inflammation and improved vasculature and kidney health, all these other beneficial effects that have to do with reducing the development of another cardiovascular event,” says Robert F. Kushner, MD, an internal medicine physician and obesity medicine specialist at Northwestern Medicine, professor of Medicine in the Division of Endocrinology and Medical Education at Northwestern University Feinberg School of Medicine and co-author of the study.

As projections show that more than half of the world’s population will be living with overweight or obesity by 2035, these medications could improve health and quality of life, and reduce healthcare costs for people living with obesity and subsequent medical complications like heart failure.

“This new era of medicine has the capability of changing our society,” says Northwestern Medicine Cardiologist Clyde W. Yancy, MD, MSc, who is also chief of Cardiology in the Department of Medicine at Feinberg School of Medicine.

Honing In on Heart Failure

Sanjiv J. Shah, MD, a Northwestern Medicine cardiologist and professor of Medicine in the Division of Cardiology at Feinberg School of Medicine, co-authored a study showing that weekly doses of semaglutide improved health outcomes and quality of life for patients with heart failure with preserved ejection fraction (HFpEF). HFpEF affects nearly half of the 5 million patients in the U.S. diagnosed with heart failure annually. “We know that obesity is tied to the HFpEF epidemic,” says Dr. Shah.

The study found that regardless of baseline health status, participants on semaglutide experienced greater weight loss and larger improvements in heart failure-related symptoms, physical limitations and exercise function. Semaglutide was also associated with improvements in all domains of the Kansas City Cardiomyopathy Questionnaire, a measure of health status that combines patient quality of life and symptoms.

Another study published in the New England Journal of Medicine, also co-authored by Dr. Shah, found that participants on semaglutide lost more weight, with a mean percent reduction in body weight of 13.3% compared to 2.6% for patients taking a placebo. At the end of the trial, compared to the placebo group, patients receiving semaglutide could walk farther, had lower levels of C-reactive protein (a biomarker for inflammation known to drive heart failure), and greater reductions in B-type natriuretic peptide (a biomarker that correlates to severity of heart failure).

“It was really remarkable to see how effective a weight loss drug it was, even in the setting of heart failure,” says Dr. Shah. “However, we were most interested in whether the drug could reduce symptoms and signs of heart failure itself. We found that patients treated with semaglutide (compared to placebo) had much greater improvements in their health status (which includes quality of life, symptoms and physical limitations). In fact, health status improved with semaglutide more than any other heart failure medical therapy tested to date. [All of this] is hopefully convincing the scientific community that obesity drives this syndrome.”

According to Dr. Shah, there are combination therapies and other medications being tested that could also make a big difference for these patients.“Semaglutide is just the tip of the iceberg,” he says.

Identifying Health Disparities and Access Challenges

As with any new therapy, many questions about implementation and availability arise: Who can access the medication, and who can’t? What are the financial and lifestyle costs?

Dr. Yancy says these new medications allow people to think differently about obesity. “[Obesity] should be treated as a disease, and these drugs allow us to destigmatize it,” he explains. “Obesity should not be a pejorative descriptor; it’s a medical condition, just like high blood pressure or diabetes.”

However, Dr. Yancy notes the clinical trials lack racial diversity, making it hard to prove that semaglutide and other GLP-1 receptor agonists will work for a variety of people.

Veronica R. Johnson, MD, an internal medicine physician who treats patients at the Northwestern Medicine Center for Lifestyle Medicine, says it’s important to raise awareness about the barriers of access to these medications, whether it’s insurance, a clinician’s lack of education around obesity treatment, stigma, race or other issues. She contributed to a commentary published in Nature Medicine, which outlines inequalities facing patients and clinicians around GLP-1 receptor agonists. Lack of insurance coverage, costs, stigma and regulations are some of the key factors she discussed.

Pursuing Further Research 

More research is still needed to understand long-term use and how weight stigma and biases experienced in society all impair the acceptance of these therapies, according to Dr. Johnson. “We know from bariatric surgery research that Black and Latino patients have less than average weight loss post operatively.  The most likely reason for this disparity is explained through social determinants of health,” she says. “We need more clinical trials that have diverse populations and samples.”

More research is also needed on the long-term impacts of these anti-obesity medications. Dr. Kushner says future research will need to explore if these medications need to be taken for life, similar to diabetes medication or statin therapy.  

“There are questions about the intensity, frequency and components of lifestyle behavioral treatment that need to be paired with medications. It’s still an area that needs more research,” he says. “Treating obesity is really difficult, and studying these drugs and being able to provide them has been a really rewarding part of my career. It’s about quality of life, it’s about hearing my patient’s stories and doing what they always wanted to do. It’s life-changing for people.”