After losing more than 20 percent of their body weight in eight months, people who stopped taking the weight loss drug Zepbound (tirzepatide) regained about half the weight within a year, according to a new study published today in JAMA.
People who continued to take the medication lost an additional 5 percent of their original body weight, for a total average weight loss of 25 percent over the 88-week study.
Tirzepatide was first approved by the U.S. Food and Drug Administration (FDA) in May 2022 under the name Mounjaro, to improve blood sugar control in adults with type 2 diabetes — but it also showed impressive weight loss results.
In November, the FDA approved tirzepatide under the new name Zepbound, for weight loss in individuals with a body mass index (BMI) of 30 or higher, and for those with a BMI of 27 or greater who also had health conditions such as high cholesterol or high blood pressure.
Tirzepatide May Be a Lifelong Drug
If you stop the medication, you regain the weight — there’s no question that will happen, says coauthor Louis Aronne, MD, a professor of metabolic research and director of the Center for Weight Management and Metabolic Clinical Research at Weill Cornell Medicine in New York City. “But that shouldn’t be surprising. Obesity is a chronic disease that needs chronic treatment for the benefit to be completely maintained,” he says.
The findings here highlight that to maintain weight loss, people should continue on tirzepatide long-term, says Fatima Cody Stanford, MD, MPH, an associate professor of medicine at Harvard Medical School and obesity medicine specialist at Massachusetts General Hospital, both in Boston. Dr. Stanford, who is also a medical reviewer for Everyday Health, was not involved in the study.
“As noted with other GLP-1 agents, weight gain happens when patients are taken off the agent. These agents act on pathways of the brain that regulate weight and food intake, and when these patients are no longer receiving treatment, they no longer have these brain pathways to regulate weight, and they regain it,” she says.
People Who Stopped Taking Zepbound Were Still 22 Pounds Lighter on Average After 1 Year
The purpose of this study was to find out if the impressive initial weight loss after the first eight months would continue beyond the period of active treatment. A total of 670 eligible participants were randomly assigned to either continue taking Zepbound for an additional year (52 weeks) or to switch to a placebo.
Throughout the trial, all participants received lifestyle counseling from a qualified healthcare professional to help them stick to a healthy 500 calories per day deficit diet and at least 150 minutes of physical activity per week.
Those who continued to take Zepbound lost an additional 5.5 percent of their weight (on top of the 20.9 percent they already lost), while those who went on placebo regained about half the weight they lost over the course of the year — meaning they were still down nearly 10 percent compared with their original weight.
In other words, at the end of 88 weeks, those who continued taking tirzepetide had lost on average 60 pounds, and those who went on the placebo maintained a 22-pound weight loss.
That amount of weight loss is still very good, says Aronne. “I think many people think that everyone will immediately regain weight; that was not the case. Of the patients who switched to placebo, 16.6 percent were able to maintain 80 percent or more of the weight they had lost,” he says.
The effects of intensive behavioral therapy on the maintenance of weight reduction weren’t evaluated, which could make a difference in preventing weight regain after coming off the drug, the authors acknowledged.
Treating Obesity Can Also Improve Hypertension, Heart Disease, and Diabetes
Obesity is a leading driver of many diseases, including high blood pressure, heart disease, diabetes, and fatty liver disease, says Aronne. “If you were to treat any of these conditions, you wouldn’t be treating any of the others, but with obesity treatment, you can address all of them, and get improvement in quality of life measures, especially physical functioning,” he says.
Participants taking Zepbound had significant improvements in BMI, cholesterol and triglyceride levels, blood sugar, and blood pressure. Some, but not all, of those advances were lost in the placebo group.
“The metabolic benefits tended to revert back towards baseline, but some, like insulin, triglycerides, and improvements in quality of life, were still significantly better. None were worse than when the trial started,” says Aronne.
Again, this is to be expected, since weight loss produced all these benefits — and when there’s not as much weight loss, there’s not as much benefit, he says.
Once People Stop Taking GLP-1s, They Will Gradually Regain Lost Weight
If the trial had continued to follow the people on placebo after a year, both Dr. Aronne and Stanford agree that those individuals would eventually regain most, if not all of the weight they lost.
“Would it take another year? We’re not sure. If they restarted the medication, would they go back to where the group who was treated went and with the same benefit? We don’t know that either, but based on our clinical experience with medication, that’s what I would expect,” says Aronne.
Weight Cycling Can Harm Health and Contribute to Obesity
“Weight cycling causes harm to your health and it contributes to obesity,” says Stanford.
Constantly losing and gaining weight — called weight cycling or yo-yo dieting — leads to adverse health outcomes, according to the Endocrine Society. Research has also linked weight cycling with risk of early death.
More Research Is Needed to Explore Long-Term Risks of Medications
These findings suggest that people may need to stay on Zepbound long-term to maintain weight loss and the associated health benefits, says Aronne.
Further studies will be needed to assess the long-term risks and benefits associated with these drugs, especially considering the potential for their lifelong use, the authors wrote.
This study is an important step in continuing to build the case for the continued insurance coverage of GLP-1 medications, so that people can maintain weight loss benefits, says Suki Singh, MD, a family medicine and obesity medicine physician and system medical director for weight management and obesity medicine at Henry Ford Health in Detroit.
But on the other hand, more research is needed to know if taking these drugs indefinitely is safe, she points out. “It’s still unknown if there are long-term complications or side effects associated with these medications, or what their impact is going to be on the gut, or [if] there’s an increased risk of C-cell tumors,” she says.
In rats, tirzepatide caused thyroid C-cell tumors but it isn’t yet known if the drug poses any risk for the increase of C-cell tumors in humans.
“Until we have more data available, it’s hard to say if these medications are the long-term answer to treating obesity,” says Dr. Singh.
