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People are likely to experience several biological and psychological changes shortly after they stop taking GLP-1 drugs like Mounjaro and Zepbound. Viktor Cvetkovic/Getty Images
  • Mounjaro and Zepbound can help qualified individuals lose and maintain weight and blood glucose levels.
  • These medicines are not recommended for short-term use.
  • Stopping them can prompt weight regain, blood sugar spikes, and increased appetite, among other side effects.

Like Ozempic and Wegovy, Mounjaro and Zepbound can help people control blood sugar levels and reduce or maintain weight.

While these GLP-1 drugs are not recommended for short-term use, people stop taking them for a variety of reasons, including reaching their weight loss goals, severity of side effects, and cost.

In fact, a recent study found that most people quit taking GLP-1 drugs within the first three months, which isn’t long enough to see their effects.

However, many people may not be aware of the changes they’ll likely experience in the days and weeks after they stop taking these medications, especially for those who quit cold turkey.

“When coming off any medication, it is essential to talk to your healthcare provider to understand the changes that may occur within your body,” says HaVy Ngo-Hamilton, PharmD, a pharmacist and clinical consultant at BuzzRx. “Many medications are safe to quit cold turkey, while certain medications require careful tapering to avoid unpleasant withdrawal effects or even harmful outcomes.”

These are the most common biological and psychological changes people experience after they stop taking Mounjaro or Zepbound.

Weight regain

While some effects of stopping Mounjaro and Zepbound are currently more anecdotal, weight regain (sometimes referred to as “Ozempic rebound“) has some data behind it.

In a 2023 randomized clinical trial, 783 participants took tirzepatide (the generic name for Mounjaro and Zepbound) for 36 weeks. Those who stayed on the drug until week 52 lost an additional 5% of body weight, while those who stopped and took the placebo regained 14% of the weight lost.

These results are consistent with those in a 2022 trial extension on semaglutide (the generic name for Ozempic and Wegovy), which suggested that people who stopped taking 2.4 mg weekly doses regained two-thirds of the weight they lost within one year of cessation.

To grasp why patients regain weight after stopping the drugs, it might help to understand how they work.

“Tirzepatide is a glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist,” Ngo-Hamilton says. “Tirzepatide stimulates GLP-1 and GIP receptors, making it the first medication in its class to target both GIP and GLP-1 receptors.”

The body naturally produces GIP and GLP-1, which Ngo-Hamilton says are responsible for:

  • Communicating with the pancreas to secrete more insulin after eating
  • Boosting insulin sensitivity
  • Controlling blood sugar production
  • Slowing stomach emptying so you feel fuller sooner and longer

Zepbound and Mounjaro help the body in these efforts but don’t make permanent changes.

“After discontinuing an anti-obesity medication, our body’s weight-promoting mechanisms fire back up,” explains Dr. Christopher McGowan, MD, ABOM, a gastroenterologist, obesity medicine specialist, and founder of True You Weight Loss. “The underlying biology has not been altered.”

Appetite can increase

Decreasing appetite and quieting food noise and cravings are among the key reasons experts say Zepbound and Mounjaro help people lose weight. As a result, a person will likely experience an increase in appetite for the same reason they experience an uptick in weight.

“When stopping tirzepatide, it is highly likely your appetite will return to what you considered normal before using the drug,” Ngo-Hamilton reiterates. “By mimicking the actions of certain natural body hormones, this medication both literally and figuratively keeps your stomach full for longer periods of time by slowing emptying after eating, increasing insulin production, and triggering feelings of satiety.”

Since a person feels hungrier sooner, they may be more likely to consume more food.

“As you increase the frequency and portion needed to satisfy your hunger, your stomach will stretch over time, requiring larger portions to feel satiated,” Ngo-Hamilton says.

This is a change that you’ll likely notice shortly after you’ve stopped taking the drug, as the half-life of tirzepatide is about one week.

“This means that within four weeks, most of the drug has exited the body,” says McGowan. “However, within one to two weeks after stopping the medication, patients may experience rebound hunger and appetite.”

Sense of taste may change

This one is less straightforward, but it’s possible that people may experience a change in food taste after stopping tirzepatide.

“Studies haven’t supported any meaningful correlation between changes in taste or food aversions as a result of taking tirzepatide or semaglutide, though there have been anecdotal accounts of this from people who use the medications,” Ngo-Hamilton says.

Again, food isn’t just about tastebuds and the stomach. The brain is involved.

“Taste involves a complex neurological process that starts with cells in taste buds and ends in key centers of the brain,” explains Dr. Jewel Osborne-Wu, MD, a Family Medicine Physician at Revolution Medicine. “GLP-1 receptors have been found along multiple parts of this pathway.”

  • Taste sensitivity. “One aspect of the disease of obesity is that there is a dulling of receptor response to taste and therefore the desire for overly sweet and salty foods is strong,” Osborne-Wu says. “With GLP-1 action causing increased taste sensitivity, the need for overly sweet and salty foods is diminished.”
  • Perception of types of taste. “Reward centers of the brain encourage increased consumption of certain flavors, especially sweetness, as this signals a quick source of energy for the body,” Osborne-Wu says. “GLP-1 action reduces the effect of these reward pathways, thereby reducing cravings for sweet foods.”
  • Genetic coding and expression of cells responsible for taste. “GLP-1 directly influences the types of cells that are expressed and, in so doing, can change the profile of taste cells such as those found in the tongue,” Osborne-Wu says.

Mood changes

The link between GLP-1 drugs and mental health is still being studied, and it can go either way.

“For example, it’s thought that mood changes may occur due to how the drugs interact with brain chemicals such as dopamine and serotonin,” Ngo-Hamilton says. “What we do know is that studies have shown that people who take Zepbound and Mounjaro for weight loss can experience mood changes – whether positive or negative.”

For instance, Eli Lilly, which makes Zepbound, cautions people to note thoughts of suicide and depression and discuss them with a doctor. Additionally, low blood sugar might cause mood changes.

The FDA is continuing to monitor for suicidal thoughts and actions in these medicines but indicated that early data does not suggest a causal link.

And data published in 2024 on drugs, including semaglutide and tirzepatide, indicated that people with diabetes who took the drugs were less likely to experience anxiety and depression than those who didn’t.

So, what might this mean for stopping?

Ngo-Hamilton says some people may experience poorer mental health.

Dr. Katherine H. Saunders, MD, DABOM, the founder and executive vice president at Intellihealth, agrees, pointing out that “weight regain, as well as an increase in hunger, cravings, [and] food noise, may cause some patients to feel anxious or depressed.”

However, others may report the opposite.

“In some cases, people have reported increased feelings of depression or thoughts of suicide while using these drugs, which may decrease or cease completely once they stop,” Ngo-Hamilton says.

Insulin spikes

While weight loss may make headlines, it’s not the only benefit of taking tirzepatide. One of the key benefits of tirzepatide — and why Monjaro got the FDA’s green light for diabetes treatment — is its ability to help with insulin levels.

“Because tirzepatide triggers insulin production and is commonly used to manage high blood sugar/type 2 diabetes, people who stop using it may experience spikes in their blood glucose levels if their bodies are unable to produce sufficient insulin without other antidiabetic medications being onboard,” Ngo-Hamilton says.

GI side effects

GI discomforts, like nausea and diarrhea, are common. Though they can taper with time, for some, they may prompt people to cease use.

“If you experienced gastrointestinal side effects while your body was adjusting to the medication, you may experience some or all of these side effects while your body adjusts to the absence of the medication,” Ngo-Hamilton says. “Generally, after stopping the drug, it may take around 25 to 30 days for it to leave the body completely.”

If side effects persist beyond this timeframe, Ngo-Hamilton recommends speaking with a healthcare professional.

Zepbound and Monjaro are intended for long-term use. Cessation can prompt a person to regain weight and appetite, as the drugs do not change a person’s biology permanently.

Some people anecdotally report feeling better mentally after stopping, while others say the opposite — potentially because the return of food noise and weight can be emotional.

Gastrointestinal discomfort experienced while taking these drugs should taper within a month of stopping. Patients are encouraged to speak with their healthcare provider if the symptoms persist longer.

“It is very important to have a detailed discussion with your provider prior to discontinuing the medication,” Osborne-Wu says.