In the face of an obesity epidemic, new developments in preventive cardiology are transforming how physicians navigate weight management and cardiovascular disease. Yet the complexity of the crisis—and a healthcare system under strain—confront Cedars-Sinai experts with an urgent question: Can they successfully optimize these recent advances and realize their full potential to improve lives?

The answer, they believe, is a qualified “yes.”

In March 2024, the U.S. Food and Drug Administration (FDA) approved the use of semaglutide, a weight loss drug, as a preventive treatment for serious cardiovascular conditions. The FDA’s action was driven by a 2023 New England Journal of Medicine study, known as the SELECT trial, that showed patients who were prescribed the drug had a 20% lower risk of death from heart attacks or stroke.

“The SELECT trial was the first published evidence we have that a weight loss drug could actually reduce the occurrence of cardiovascular events in patients with obesity and ischemic heart disease,” said Martha Gulati, MD, director of Preventive Cardiology at Cedars-Sinai and a renowned expert in the field. “Our physicians are committed to providing evidence-backed solutions for those who need them most.”

Physicians and surgeons at Cedars-Sinai are leading the charge as patient advocates, working to secure access to GLP-1 receptor agonists such as semaglutide so patients can reap their cardiovascular benefits. At the same time, guided by the science, they see the drugs as just one component of a broader and more comprehensive strategy to combat obesity and lower cardiovascular disease (CVD) risk.

Read: A Better Model of Heart Disease Prediction

In Cedars-Sinai clinics, the results have been definitive: GLP-1 drugs are dramatically more effective than earlier classes of weight loss medications, among them lipase inhibitors like orlistat. By comparison, semaglutide achieves far greater weight loss with more tolerable side effects.

“Semaglutide really works: On average, our patients are losing about 15% of their body weight in a year and a half, whereas with orlistat, it was less than 5%,” said Amanda Velazquez, MD, director of Obesity Medicine at Cedars-Sinai. “Semaglutide also enables some of our patients with Type 2 diabetes to discontinue insulin, which we know can be weight promoting, and in some cases it’s allowing patients with high blood pressure to reduce the medications they need to keep their blood pressure down.”

The impact on overall wellness—and the implications for medication management—are considerable. By prescribing one medication upstream, physicians can improve multiple downstream conditions with positive ramifications for heart health.

Still, there are limits to what the drug can accomplish, cautioned Gulati, who is also the Anita Dann Friedman Chair in Women’s Cardiovascular Medicine and Research at Cedars-Sinai.

“Semaglutide isn’t necessarily a substitute for other heart-related medications,” she said. “Patients’ blood pressure and cholesterol levels might improve from taking it, and that can obviously help reduce CVD risk, but this drug does not replace statins.”

Read: How to Choose a Weight Loss Path

But access and availability present barriers to the emergence of semaglutide as the next blockbuster drug for preventing cardiovascular illness. Most insurance plans do not cover GLP-1 drugs for CVD prevention.

“The drug is simply inaccessible for many patients, which is very frustrating,” Gulati said. “As a society, we need to ask ourselves: Do we want patients to get CVD and only then treat them? Or should we treat them earlier so we can prevent CVD events?”

Valentina Obreja, DNP, a nurse practitioner in the prevention clinic at the Barbra Streisand Women’s Heart Center in the Smidt Heart Institute at Cedars-Sinai, sees every day how lack of insurance coverage impacts patients’ lives.

“We have many more patients who could benefit from semaglutide than are currently taking it because the roadblocks to prescription are so significant,” she said. “To be eligible for coverage, patients need to have obesity with a body mass index (BMI) above 30 or be overweight and have established heart disease that is obesity related. That leaves out a huge population of patients who are trying to be proactive about CVD prevention. It’s a constant fight with the insurance companies.”

Read: Preventing Heart Disease in Women

“Many of our patients have complex medical conditions and require a multipronged treatment plan. The majority of visits at our Center for Weight Management and Metabolic Health are focused on patient education, helping patients realize that obesity is a disease and that there isn’t always one straightforward solution,” Velazquez said.

Changes to exercise and diet are important parts of the equation and can reduce body weight by approximately 10%, according to Gulati. Bariatric surgery can also yield significant results.

“Bariatric surgery is the most effective and longest-lasting treatment for morbid obesity, and it’s been shown to decrease the risk of premature death,” said Kulmeet Sandhu, MD, associate director of Minimally Invasive and Bariatric Surgery at Cedars-Sinai. “Surgery is also effective for the improvement of comorbidities like CVD, high blood pressure, sleep apnea and diabetes.”

In reality, many patients with a higher BMI or obesity need a combination of medication, lifestyle modifications and surgery to maximize their cardiovascular benefits.

Cedars-Sinai patients benefit from the integrated expertise of preventive cardiologists, bariatric surgeons, dietitians, exercise physiologists and others working together to determine the best treatment method, Gulati said.

This high-quality collaboration at Cedars-Sinai translates to tangible patient gains. Joint clinic visits with patients enable Gulati, Velazquez and their colleagues to evaluate patients’ needs through the lens of their own specialty and then widen the lens by looping in other experts.

“Our partners in electrophysiology care for many patients with atrial fibrillation, and our colleagues who treat heart failure often reach out to us, as preventive cardiologists, to ask for our help in treating patients’ excess weight,” Gulati said. “The more we pool our efforts and resources as healthcare providers, the better off these patients become.”

Velazquez agreed.

“As a team at Cedars-Sinai, we leverage all the tools in our toolbox to make inroads against these complex diseases,” she said.

Ongoing research continues to shed light on the potential to leverage GLP-1 agonists on disease states—and also aims to elucidate the mechanisms of drug action.

“Countless trials target the brain, the gut and adipose tissues, and we’re also continuing to learn more about semaglutide and the way it impacts cardiac functioning,” Gulati said.

Newer weight loss drugs demonstrating even more impressive results are entering the market and coming down the development pipeline. Although none have yet been approved for the management of CVD risk, ongoing studies are finding associations between these drugs and lowered CVD risk.

Tirzepatide, a dual GLP-1/GIP receptor agonist, acts through a different mechanism than semaglutide and has been FDA approved for chronic weight management in adults with obesity. Results from the SUMMIT trial—released at the November 2024 American Heart Association conference—demonstrated that tirzepatide reduced cardiovascular mortality and heart failure endpoints in people with obesity and heart failure with preserved ejection fraction.

Clinical trials treating obesity are also underway on retatrutide, a triple agonist that may carry reduced side effects.

“Whether we’re talking about weight management or lowering CVD risk—or both—the benefits could be enormous,” Gulati said.

As obesity medicine enters a new era and the use of semaglutide becomes more widespread, physicians would do well to prescribe the drug under watchful supervision, Velazquez said.

“Every medication comes with side effects, and with semaglutide, the most common are gastrointestinal-related. But through judicious dosing, monitoring the patient closely, and implementing dietary and lifestyle changes, we can mitigate them,” she said.

Prescribing cautiously can help avoid other unwanted outcomes, as well.

“There’s a risk of sarcopenia while on these drugs, and we emphasize the importance of resistance training, muscle strengthening and eating sufficient amounts of protein,” Gulati said.

Despite its potential side effects, semaglutide shows enormous promise for patients at Cedars-Sinai and beyond.

“We’re talking about substantially reducing the rate of major cardiovascular events,” Velazquez said. “This drug could play a vital role in helping us save people’s lives.”