The Health Risks and Benefits of Weight-Loss Drugs

The newest weight-loss drugs, Wegovy and Zepbound, are incredibly popular. But doctors are still learning about all of the ways they affect the body—both helpful and harmful—beyond reducing weight.

In report published in Nature Medicine, Dr. Ziyad Al-Aly, assistant professor of medicine at Washington University School of Medicine in St. Louis, and his colleagues performed a comprehensive analysis on the health outcomes associated with the drugs known as GLP-1 receptor agonists. These medications began as diabetes treatments to lower blood glucose levels and have now been approved to help people without diabetes lose weight. [time-brightcove not-tgx=”true”]

But because they have been used for longer as diabetes treatments, Al-Aly’s team studied the health records of more than two million people with diabetes in the Veterans Affairs database, some of whom were taking the GLP-1 medications and some who took other diabetes treatments. They tracked health outcomes over about four years for 175 different conditions, including infections, substance-use issues, Alzheimer’s disease, arthritis, and gastrointestinal disorders.

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The group found that people taking the GLP-1 medications had a lower risk of a number of health conditions, including Alzheimer’s disease and dementia, addiction, seizures, blood-clotting problems, heart conditions, and infectious diseases, compared to people taking the other types of diabetes treatments. The people taking the GLP-1 drugs also had increased [also here] GI-related issues, low blood pressure, and arthritis, as well as certain kidney conditions and pancreatitis—most of which are already known side effects of the medications.

“What this paper shows is that treating obesity and metabolic syndrome likely has a broad health profile,” says Al-Aly. “We know obesity is bad for many, many things, and now we have empiric evidence that treating obesity produces good health benefits across the board beyond just reduction in weight. But there are also risks, and we hope these findings prompt discussion with people and their providers.”

Many of the health benefits listed in the new paper are known. The U.S. Food and Drug Administration (FDA) recently approved adding to Wegovy’s label that the drug can also reduce the risk of heart events by 20% in people with obesity , for example. In Dec. 2024, the FDA also added to Zepbound’s label that it can reduce the symptoms of obstructive sleep apnea.

Other health benefits, including the reduction in Alzheimer’s disease are currently being studied by the drugs’ manufacturers. (In the current analysis, Al-Aly found that people taking the drugs had a 12% lower risk of the neurodegenerative disorder.)

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Many tissues in the body have receptors for GLP-1, a hormone, which explains its multiplicity of health effects. The study included people taking different types drugs in this category—semaglutide (Wegovy and Ozempic), and tirzepatide (Mounjaro and Zepbound). While tirzepatide targets two hormones—GLP-1 and GIP—Al-Aly says the predominant effect of tirzepatide is likely on GLP-1.

Canvassing all of the health effects of a new drug category like GLP-1s could be a novel way for agencies like the FDA to get an early understanding of a new medication’s potential benefits and harms. “We hope we’ve provided an example for how these new technologies and statistical methods could be used to help us build a map of a new drug’s landscape,” says Al-Aly.

Since all of the people in the study had obesity, it’s not clear to what degree the health benefits were related to people losing weight, and which effects were potentially independent of weight. “You can conceptualize obesity as the mother of all ills,” says Al-Aly. It could be that “people get on GLP-1s to lose weight, and as a consequence of the weight loss, feel better.” But it’s also possible that GLP-1s are benefiting the body in other ways, he says.

For instance, there are GLP-1 receptors in brain regions that regulate impulse control and reward. That’s how scientists believe these medications suppress appetite: by dampening the reward signaling associated with food. Similar pathways could explain why the medications have suppressive effects on addictions to alcohol, tobacco, cannabis, and opioids. GLP-1s also have anti-inflammatory effects, which can stabilize the function of cells that line the blood vessels and help to minimize clot formation, Al-Aly says.

Scientists like Al-Aly are only starting to understand the widespread effects these medications have on the body. Questions remain: The study wasn’t designed to test whether different doses of the drugs could provide greater health benefits, for example. And in coming years, newer formulations that target three hormones in the same family—instead of one or two—might offer even more potent health benefits.

“The story of GLP-1s is really being written every day,” says Al-Aly. “Our group and others have several more years—decades, even—to really flesh out [that story] completely.”