You’ve probably heard the stories of dramatic weight loss: Semaglutide, the active ingredient in Ozempic and Wegovy, can help people lose 15 percent of their body weight. Tirzepatide, sold under the brand names Maunjaro and Zepbound, may be even more effective at helping people lose weight.
These drugs, known as GLP-1 agonists, were originally developed to control diabetes. But there’s growing evidence that they may have health benefits beyond just keeping weight in check. They appear to promote heart health, protect the kidneys, improve sleep apnea, and lower the risk of certain cancers linked to obesity. Recent studies suggest they may also treat addiction and slow the cognitive decline associated with dementia. As researchers test these drugs for a variety of conditions, they’re trying to solve the mystery of how they work in the body. And there are a few theories.
“Many in the medical community are beginning to think of these drugs as health-enhancing drugs rather than just weight-loss or anti-obesity drugs,” says Harlan Krumholtz, a cardiologist and professor at the Yale School of Medicine.
In March, Novo Nordisk’s Wegovi became the first weight-loss drug approved to also help prevent serious heart problems in people with cardiovascular disease. In an international trial of more than 17,600 overweight patients, weekly Wegovi injections significantly reduced the risk of serious heart attacks. Researchers followed participants for an average of three years and found that those who took Wegovi were 20% less likely to suffer a heart attack, stroke or die from other cardiovascular causes.
Eli Lilly & Co., which makes tirzepatide, is also looking to expand Zepbound’s uses after the company said this month that its weight-loss drug improved symptoms and reduced hospitalizations by 38% in obese heart failure patients.
One in four people die from heart disease each year in the United States, with obesity being an increasingly important contributing factor. Being overweight can lead to high blood pressure and elevated cholesterol levels, which increase the risk of heart attack and stroke. Weight gain can also affect the function of the heart muscle, increasing the risk of heart failure. It may not be surprising that medications that help with weight loss also improve heart health. However, there are reasons to believe that there are other factors at play besides weight loss.
“When we first saw the results, we wondered if it was just about weight loss,” Krumholz says, “but we found that greater weight loss doesn’t necessarily translate to greater benefit.”
In trials of heart disease patients, Wegobi reduced blood pressure, cholesterol levels, heart rate and cardiac inflammation before participants reached maximum weight loss. What’s more, the drug seemed to reduce major heart attacks regardless of how much weight they lost. The same was true for patients with heart failure. All of this leads Krumholz to think that the drug is, at least in part, acting on the cardiovascular system in a different way. “That’s the big question,” he says. “What is the exact mechanism of effect?”
Semaglutide and tirzepatide work by mimicking the action of GLP-1, a hormone that occurs naturally in the body. They act on GLP-1 receptors in the pancreas to stimulate the release of insulin after meals, helping people with diabetes to control blood sugar levels. They also bind to GLP-1 receptors in the brain, making people feel fuller and helping them eat less.