People Who Stop Taking Zepbound Will Likely Gain Weight Back, Study Finds

  • Last month, the FDA approved Zepbound, a GLP-1 agonist, as a weight loss medication.
  • A new study found that when people come off the medication, they may regain some of the weight they lost while on it.
  • Experts recommend speaking to a trusted healthcare professional in order to choose the best weight loss treatment for your unique circumstance.

People who stop taking Zepbound (tirzepatide) may regain a majority of the weight they lost while taking the drug, a new study finds.

New research published earlier this month in JAMA raises questions about who should take Zepbound and whether some people will have to be on the drug for the rest of their lives to see benefits.

The research was sponsored by Eli Lilly and Company, the pharmaceutical company that makes Zepbound.

“I think the idea that obesity is a chronic disease and needs chronic treatment—that’s one of the messages of this study,” Louis Aronne, MD, an endocrinologist at Weill Cornell Medicine and an author of the new study, told Health.

The study highlights that doctors need to approach obesity as a condition that needs to be monitored and maintained throughout a person’s lifetime, “the same way we treat any other chronic metabolic disease,” Aronne explained.

Though the study suggests stopping the drug may cause weight gain for some, Zepbound—which belongs to a class of medications called glucagon-like peptide-1 (GLP-1) agonists—can be life-changing for some people with obesity who have not been able to lose weight by way of behavioral changes, W. Scott Butsch, MD, MSc, director of obesity medicine at the Bariatric and Metabolic Institute of Cleveland Clinic, told Health.

“These medications, for the right people, can really transform somebody’s life,” he said.

Butsch explained that these medications may be able to enhance some people’s quality of life in addition to improving certain health metrics, such as their blood pressure and cholesterol readings.

Here’s who Zepbound may be best suited for, how it can help people with obesity, and what doctors—and patients—should consider before trying it.

Woman stepping on scale

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Most People May Regain Weight After Stopping Zepbound

Zepbound—a brand name of the drug tirzepatide—was approved as a weight loss medication by the Food and Drug Administration (FDA) last month.

The drug showed promise in a 2022 phase 3 clinical trial which found it could help people lose 20% of their body weight over the course of 72 weeks.

Aronne explained that the research team of the new study wanted to see how patients fared after they stopped taking the drug.

“This study was [designed] to study that issue, to see if the disease relapsed and, if so, over what time frame,” he said.

His team analyzed data from 670 participants—the majority of whom were female and white—who took the drug for 36 weeks and saw an average weight loss of 20.9% of their body weight. The average age of participants was 48, and they lived in Argentina, Brazil, Taiwan, and the United States.

After the 36-week mark, some of the participants were given a placebo, while the rest continued taking Zepbound for another year.

Those who took Zepbound saw an additional weight loss of 5.5% of their body weight, while those who started taking the placebo regained 14% of their weight.

Aronne believes that if the people who took the placebo continued to take the placebo after the year was up, they’d probably continue to regain more weight.

“If you waited another year, would they regain more weight? I absolutely believe they would,” he said.

It’s important to note that not everyone given the placebo regained as much weight back.

Aronne said it’s not yet clear why some participants were able to keep most of their weight off, and what may have triggered the weight gain for others.

He explained that, while the field of obesity medicine is quickly evolving, experts still need to nail down how newer medications (like tirzepatide) can best serve patients. It’s still not clear when—or if—people should be tapered off Zepbound.

It’s also worth noting that, given the results of the study, patients could be tempted to try Zepbound again after coming off it if they notice they’re gaining weight.

“[The findings of the new report] suggest that maybe people, if they stop the medicine and [re]gain weight, they will restart it,” he said. “Those are the things that need to be sorted out in future research.”

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Deciding Whether or Not Zepbound Is For You

To qualify for Zepbound, a person needs to have a body mass index (BMI) of 30 or higher, or a BMI of 27 or higher with a comorbidity. This comorbidity could be sleep apnea, high cholesterol, hypertension, or another health condition.

Zepbound isn’t the only new medication approved for weight loss—whether it gets prescribed instead of another medication often comes down to whether a person’s insurance will cover it, Aronne explained.

Before taking Zepbound, it’s important to consider the weekly injection’s possible side effects.

“There are definitely side effects: gastrointestinal [issues]; where you inject you can get irritation, theoretical side effects [like] thyroid cancer,” Aronne said.

But, overall, experts haven’t found Zepbound—and the other obesity medications that have come out in recent years—to be unsafe.

“Medicines in these categories have been around for 18 years, since 2005, and as time has gone on, I think we’re seeing they may be safer than we thought,” Aronne said.

Zepbound and other GLP-1 agonists haven’t been available long enough to know whether there are serious complications associated with multi-decade use. But experts say they’ve seen many success stories.

“I’ve had patients who’ve been on these drugs 15 years and have done perfectly fine,” Butsch said.

What remains to be seen, Aronne explained, is whether there are side effects to starting, stopping, and then starting the medications again.

In the meantime, if you are thinking of taking a GLP-1 agonist, it’s in your best interest to see an obesity specialist, as not all physicians know the best practices of obesity medicine, Butsch explained.

“Right now, you’re getting a lot of medical providers who may not have any training in obesity and not know how to manage patients with obesity,” he said.

This is important considering the nuance involved in prescribing GLP-1 agonists and helping people who are taking them.

“I’ve had people on [one of these medications] and I’ve weaned them off, and they’ve maintained their weight,” Butsch said. “When you’re in the care of an obesity provider like myself, who is fellowship trained in this disease, we manage patients a lot differently” than other physicians.

It’s important to talk with a healthcare provider about how long you may need to take the medication, as well as which option they think will be best for you and why that is, Butsch explained.

You should also speak with your doctor about any side effects you experience after starting the medication.