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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 brandnames Zepbound and Mounjaro is now available in US pharmacies indicated for type 2 diabetes treatment and obesity.
  • Patients who take the drug have shown dramatic weight loss.
  • Findings from a new clinical trial now shows what happens when patients stop taking the drug.

The potent weight-loss drug Zepbound (tirzepatide) has led to patients losing up to 25% of their body weight — what happens when they stop taking it?

Zepbound is finally arriving in US pharmacies this month. The drug, which shares the same active ingredient, tirzepatide, as the type 2 diabetes medication Mounjaro, is now 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, new research published in JAMA, appears to answer some of those 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, the patients 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.

After the first 36 weeks, however, outcomes were dramatically different for those who continued on the drug and those who got the placebo. Patients that remained on tirzepatide went on to lose an additional 5% of their body weight over the next 52 weeks. Those that got the placebo regained 14% of their body weight.

“This is an excellent study and it confirms what we see in practice. 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,” Dr. Dan Azagury,, 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.

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

For tirzepatide, the data is clear: those that continued taking the drug saw much more significant results, 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 Dr. Caroline Apovian, 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:

Tirzepatide (Zepbound, Mounjaro) can result in dramatic weight loss (25% of body weight).

However, long-term studies of its affects haven’t yet been conducted.

Overweight and obese patients could potentially have to take the drug for the rest of their lives.

New research indicates that patients who stopped taking tirzepatide after one year regained about 14% of the weight they lost.