How Much Weight Comes Back After You Stop Using a Weight-Loss Drug?

Zepbound, the newly approved weight loss drug, hit the market this month. People seeking out the medication may have to stay on it for the foreseeable future — potentially, for the rest of their lives — if they want to keep the weight off, new research confirms.

A study published Monday followed 670 people who had taken tirzepatide, the compound in Zepbound and the diabetes drug Mounjaro, for 36 weeks. Eli Lilly, the company that makes both drugs, funded the study. Tirzepatide regulates insulin levels and slows down the emptying of the stomach. It also acts on areas of the brain that control hunger and appetite. As a result, people can lose significant weight: On average, the study participants lost around 20 percent of their body weight during that time.

After that, half of the participants continued to take a high dose of tirzepatide for a year while the other half received a placebo shot. Those in the study also underwent lifestyle counseling, ensuring that they were eating fewer calories and exercising regularly.

People who continued taking tirzepatide for an additional year lost, on average, another 5.5 percent of their body weight. Those who were switched to the placebo, however, gained 14 percent of their body weight on average. Those on the placebo also tended to have higher cholesterol, blood sugar and blood pressure than they did while taking tirzepatide, said Dr. Louis Aronne, the lead author on the study and the director for the Comprehensive Weight Control Center at Weill Cornell Medicine.

None of this surprises the doctors who prescribe these drugs.

“We wouldn’t give someone a blood pressure medicine and be like, ‘Great, your blood pressure’s better, you should go off it’,” said Dr. Michelle Hauser, obesity medicine director of the Stanford Lifestyle and Weight Management Center. “Somehow people have this magical thinking around obesity, like you’re going to take this drug and it’s going to cause weight loss and just stay that way.”

Research has shown similar outcomes for those who take semaglutide, the compound in the diabetes drug Ozempic and weight loss drug Wegovy.

People in the placebo group did not regain all the weight they lost in the first 36 weeks of the study. It’s not clear whether they kept some weight off because of a lingering effect of tirzepatide, Dr. Aronne said, or if the lifestyle counseling played a role.

Still, weight gain is often a reality for the many patients who want to come off these medications, said Dr. Melanie Jay, director of the N.Y.U. Langone Comprehensive Program on Obesity. The side effects can be taxing, especially as people first begin the medications: Fifty-three people dropped out of the trial because of side effects such as nausea, diarrhea and constipation.

Cost is also a factor — insurance coverage can be spotty, and the list price of Zepbound is over $1,000 a month, though some patients end up paying less at the pharmacy counter. Often, patients struggle to find the medications in the first place — some doses of Wegovy and Ozempic are in shortage, and Mounjaro has also faced supply challenges over the last year.

And some patients just don’t want to deal with injecting themselves indefinitely.

“Nobody wants to take medicine forever,” Dr. Jay said. “For anything.”

Tirzepatide and drugs like it are considered long-term medications, but there is not yet robust data on what happens when people take them for decades. Ozempic, Wegovy, Mounjaro and Zepbound all belong to a single class of drugs that has been on the market for less than 20 years. “In the grand scheme of drugs, that’s a really short period of time,” Dr. Hauser said.

For now, doctors said they try to balance the side effects and possible risks of these medications with the health concerns that come with untreated obesity.

But, they acknowledged, the only way to maintain the benefits of weight loss drugs may be to stay on them.

“If a patient wants to go off the medicine, we’ll try. But we also say what the results are — so far, it seems like most people are going to gain weight back,” Dr. Jay said. “And that’s not your fault. That’s because obesity is a disease, and this medicine is helping to address it.”