You’ve heard the dramatic weight loss stories. Semaglutide, the active ingredient in Ozempic and Wegovy, can help people lose 15 percent of their body weight. Tirzepatide, sold under the brand names Mounjaro and Zepbound, may be even more effective at shedding pounds.
Known as GLP-1 agonists, these drugs were originally developed to help control diabetes. But there’s increasing evidence that they have other health benefits, beyond controlling weight. They seem to boost heart health, protect the kidneys, improve sleep apnea, and lower the risk of certain obesity-related cancers. Recent studies have also hinted at their potential to treat addiction and even slow the cognitive decline that comes with dementia. As researchers test these drugs for various conditions, they’re trying to untangle the mysteries behind how exactly they’re working in the body—and they have a few theories.
“Many of us in the medical community are really beginning to think about these drugs as health promotion drugs, not just weight loss drugs or even anti-obesity drugs,” says Harlan Krumholz, a cardiologist and professor at Yale University School of Medicine.
In March, Novo Nordisk’s Wegovy became the first weight loss medication to also gain approval to help prevent serious heart problems in people with cardiovascular disease. In an international trial of more than 17,600 people with excess weight, weekly injections of Wegovy significantly reduced the risk of a major cardiac event. Researchers followed participants for an average of three years and found that those who took Wegovy were 20 percent less likely to die of a heart attack, stroke, or other cardiovascular cause.
Eli Lilly, which makes tirzepatide, is also looking to expand Zepbound’s uses. The company announced this month that its weight-loss drug improved symptoms in heart failure patients with obesity and led to a 38 percent reduction in hospitalizations.
One in every four deaths each year in the United States is due to heart disease, and obesity is increasingly a factor. Excess weight can cause high blood pressure and cholesterol, which increases the risk of heart attack and stroke. Weight gain can also affect how the heart muscle functions, increasing the risk of failure. It’s perhaps no wonder then that a drug that helps people lose weight would also improve heart health. But there are reasons to think there are other factors at play beyond weight loss.
“When we first saw the results, we wondered, is this simply about weight loss?” Krumholz says. “But what we’re seeing is that having more weight loss doesn’t necessarily translate into more benefit.”
In the trial of people with heart disease, Wegovy lowered blood pressure, cholesterol levels, heart rate, and heart inflammation before participants reached their maximum weight loss. What’s more, the drug seemed to reduce major cardiac events regardless of how much weight they lost. The same was true for heart failure patients. This all suggests to Krumholz that the drug is, at least in part, working on the cardiovascular system in some other way. “This is the big question,” he says. “What is the exact mechanism of benefit?”
Semaglutide and tirzepatide work by mimicking the action of GLP-1, a hormone found naturally in the body. These drugs act on GLP-1 receptors in the pancreas to trigger the release of insulin after eating, which helps control blood sugar levels in people with diabetes. They also bind to GLP-1 receptors in the brain to make people feel full, leading them to eat less.
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