The class of weight-loss drugs including semaglutide, sold as Wegovy, have become immensely popular new treatments for obesity. One key factor in their effectiveness is that people need to take them indefinitely—but in practice, many don’t. A recent JAMA Network Open analysis found the vast majority of people quit taking these drugs within two years—such stops in treatment often reverses weight loss and health gains. Many people who use these drugs, and clinicians who prescribe them, are questioning how sustainable they are—and what quitting them might do to long-term health.
Growing evidence shows that many people can be considered overweight and healthy, but the relationship between health and weight is complex. Obesity can be associated with an increased risk of severe illness. The new medications, technically known as glucagon-like peptide 1 (GLP-1) receptor agonists, are used to promote substantial weight loss, cause a host of cardiometabolic improvements and treat type 2 diabetes. (Drugs for the latter include a form of semaglutide sold as Ozempic.) But when a person who had been taking one of these medications stops, the hunger cues it had suppressed often come raging back, which causes the weight to return. Other health benefits of the drugs, such as reduced blood pressure, also tend to bounce back after stopping treatment. Some evidence suggests that certain cardiometabolic benefits may persist but only modestly.
The new study surveyed more than 120,000 people, with and without type 2 diabetes, who were taking a GLP-1 medication. All were considered overweight or had obesity, and 61 percent had type 2 diabetes.The researchers found that half of the participants stopped treatment within a year of starting it, and nearly three quarters did so by the second year. The drop-off was even higher among those without type 2 diabetes: 85 percent quit after two years. The study did not investigate the effects of ceasing to use a GLP-1 medication, but previous human investigations have found that regaining weight is almost inevitable.
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These drugs work by mimicking gut hormones that slow digestion and signal to the brain that the body is full, ultimately curbing the urge to eat. But “the food noise comes back when they stop the medications,” says Janice Jin Hwang, an associate professor of medicine and chief of the division of endocrinology and metabolism at the University of North Carolina School of Medicine.
Keeping weight off isn’t as simple as ignoring food cravings; some research suggests that the human body doesn’t seem to like losing weight and actively works against it. One explanation for this is what researchers call the set point theory, which suggests that each person has a specific weight range their body naturally tries to maintain. “When you start to lose weight, your body actually adapts to try to hold on to the weight,” Hwang explains. A cascade of biological responses kicks in as t…
