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Zepbound and Mounjaro are GLP-1 drugs that can lead to weight loss. Halfpoint Images/Getty Images
  • Tirzepatide, sold under the brand names Zepbound and Mounjaro, is available in U.S. pharmacies for the treatment of type 2 diabetes and obesity.
  • People who take the GLP-1 drug have experienced significant weight loss.
  • Findings from a clinical trial show what happens when people stop taking the drug.

The potent weight-loss drug Zepbound (tirzepatide) is associated with up to a 25% reduction in body weight, but what happens when people stop taking it?

Now that Zepbound has finally arrived in U.S. pharmacies, it has become widely available.

The drug, which shares the same active ingredient, tirzepatide, as the type 2 diabetes medication Mounjaro, is approved for individuals with overweight and obesity.

Prior studies have demonstrated that tirzepatide can be even more effective for weight loss than semaglutide, the active ingredient in Ozempic and Wegovy.

However, the novelty of the drug means that no long-term studies have yet been conducted. And questions about how long patients are expected to continue taking the drug and what happens when they stop continue to arise.

Now, research published in JAMA Network appears to answer some of these questions.

The study, which was sponsored by Eli Lilly, the maker of Zepbound and Mounjaro, looked at whether patients who had taken tirzepatide for 36 weeks were able to keep weight off if they stopped taking the drug for one year.

In the study 670 participants took part in the phase 3 randomized, double-blind, placebo-controlled trial, considered the “gold standard” for clinical trials.

The study followed participants who were prescribed tirzepatide for 36 weeks. After the 36-week mark, subjects were split evenly into two groups: one continued to receive the drug, while the other was given a placebo shot. The two groups were then followed for an additional 52 weeks.

During the first 36 weeks of the trial, patients lost, on average, about 20% of their body weight.

Tirzepatide, like the similar drug semaglutide, works by slowing down digestion and increasing feelings of fullness and satiety.

However, after the first 36 weeks, outcomes were dramatically different for those who continued on the drug and those who received the placebo.

Participants who remained on tirzepatide went on to lose an additional 5% of their body weight over the next 52 weeks. Those who got the placebo regained 14% of their body weight.

“This is an excellent study, and it confirms what we see in practice,” Dan Azagury, MD, section chief of Minimally Invasive and Bariatric Surgery and medical director for the Bariatric and Metabolic Interdisciplinary clinic at Stanford University, told Healthline. Azagury wasn’t involved in the study.

“The majority of patients will regain weight if you stop the medication. There are some strategies to maximize the chances of being able to keep the weight off when you stop, but still, the majority of patients will regain a significant amount of weight,” Azagury continued.

In terms of weight-loss management, the ability to keep the pounds off and not just the amount lost, the results are even starker: nearly 90% of the tirzepatide group maintained the majority (80% or more) of their weight loss over 88 weeks, but only 16.6% of those that received the placebo were able to keep it off.

The findings are similar to other studies conducted on semaglutide, which have confirmed what some have dubbed “Ozempic rebound.”

A 2022 study found that after one year, people who stopped taking the drug regained about two-thirds of the weight they had lost.

The data for tirzepatide are clear: Those who continued taking the drug saw much more significant results, and even the group that stopped still experienced some benefits at the 88-week mark.

Both groups received lifestyle and weight-loss counseling, but it is unclear whether the weight loss in the placebo group was from lifestyle changes, residual effects from the drug, or both.

The tirzepatide group also showed additional benefits over the placebo group, including improved A1C, fasting glucose, insulin, and blood pressure.

Experts who spoke to Healthline said the findings are indicative of something else as well: the need to treat obesity like the chronic disease that it is.

“Obesity is a disease and not a matter of willpower. We need to move forward and reduce the stigma associated with this disease so that people suffering can get the treatment they need without shame,” said Caroline Apovian, MD, a professor of Medicine at Harvard Medical School and the co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital. Apovian wasn’t affiliated with the research.

For Apovian, treating obesity is analogous to treating another common, chronic condition: high blood pressure. While lifestyle changes like diet and exercise can help with high blood pressure, they aren’t always enough. For most people with high blood pressure, the realization that they will be taking an anti-hypertensive for the rest of their lives is almost inevitable.

“Why aren’t we getting this realization for obesity?” asks Apovian.

“We tell our patients that if they start they should be ok to potentially continue lifelong. Not all of them will, but you need to be ok with the possibility of this being lifelong treatment,” said Azagury.

There are side effects of tirzepatide, these can include the following:

Serious side effects of tirzepatide can include: