Zepbound side effects and how to avoid them

In this article:

• Common side effects of Zepbound
• Serious side effects of Zepbound
• How soon do Zepbound side effects start?
• How long do Zepbound side effects last?
• What are the long-term side effects of Zepbound?
• Zepbound interactions
• Safety measures while using Zepbound
• How to avoid Zepbound side effects
• How to treat side effects of Zepbound

In this article

• Common side effects of Zepbound
• Serious side effects of Zepbound
• How soon do Zepbound side effects start?
• How long do Zepbound side effects last?
• What are the long-term side effects of Zepbound?
• Zepbound interactions
• Safety measures while using Zepbound
• How to avoid Zepbound side effects
• How to treat side effects of Zepbound

Zepbound (tirzepatide) is an injectable prescription medication in the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist class of drugs. It’s approved by the Food and Drug Administration (FDA) to support chronic weight management in adults when paired with diet and exercise. It’s also approved to treat obstructive sleep apnea (OSA) in adults with obesity. While it can be an effective tool for weight loss, like all medications, it comes with the risk of side effects. Some are common and manageable, while others may be more serious and require medical attention. 

Common side effects of Zepbound

Like other GLP-1 medications, Zepbound most often causes gastrointestinal (GI) issues. These side effects are typically mild to moderate, especially when just starting the medication. Some side effects may be more common the higher the dose of Zepbound.

According to clinical trials, the following are the most common side effects of Zepbound among patients who were treated with a 10 mg dose: 

• Nausea (29%)
• Diarrhea (21%)
• Constipation (14%)
• Vomiting (11%)
• Abdominal pain (9%)

Other side effects of Zepbound include allergic reactions, low blood pressure (hypotension), hair loss, and injection site reactions.

RELATED: What to know about Zepbound and tirzepatide

Serious side effects of Zepbound

While uncommon, Zepbound can also cause more serious side effects. These require medical attention and should not be ignored. Watch for the following:

• Severe or prolonged GI side effects (e.g., diarrhea, stomach pain, or constipation)
• Allergic reactions
• Low blood sugar (e.g., fatigue, lightheadedness, dizziness, or fainting)
• Suicidal behavior and ideation

Zepbound also carries the risk of acute (short-term) kidney injury, gallbladder problems, gallstones, and pancreatitis. It also increases the risk of thyroid C-cell tumors, also called medullary thyroid cancer. 

Jennifer Brown, MD, board-certified obesity medicine specialist and obesity expert for MyObesityTeam, shares her clinical experience: “The most serious side effects that I see in patients that are associated with Zepbound include vomiting, abdominal pain, gastroparesis (bowels slow down too much), dehydration, and problems with the gall bladder/pancreas,” she says. 

Certain populations taking Zepbound may have an increased risk of complications with other health concerns. 

• People with Type 2 diabetes have a higher risk of retinal injury, or diabetic retinopathy. 
• People taking Zepbound and having general anesthesia may have a higher risk of pulmonary aspiration, or inhaling liquid, saliva, or stomach acid into the lungs. 
• People taking blood pressure medications have a higher risk of developing low blood pressure (hypotension) compared to people not on blood pressure drugs. 
• People with prolonged or severe GI side effects may be prone to dehydration, which increases the risk of acute kidney injury.

How soon do Zepbound side effects start?

Many people notice side effects soon after their first few doses or after increasing the dose of Zepbound. “While each person may experience different timing of side effects, they generally start within a few hours of the injection and last for two to three days,” Dr. Brown says. 

Pamela Tambini, MD, medical director at Engage Wellness in Acton, Massachusetts, shares that common side effects can appear later as well. They can “start within a few days of treatment starting but fade within two to four weeks at a stable dose,” she says. “Serious, but rare, side effects can appear at any point and duration depends on the complication,” she adds. 

How long do Zepbound side effects last?

For most people, side effects improve as the body gets used to the medication. Some may last just a few days, while others can continue for weeks. As mentioned, most side effects resolve after a few weeks on a stable dose. This was also the experience reported from clinical trials, where the majority of GI side effects decreased over time once the patient adjusted to their maintenance dosage. 

If you experience severe or prolonged side effects, contact your healthcare provider.

What are the long-term side effects of Zepbound?

While most side effects of Zepbound occur early in treatment, some may persist or develop over time. “Tirzepatide has not been around long enough to know for certain what long-term side effects can occur,” Dr. Brown says.

However, clinical trials show that people on tirzepatide may experience small increases in heart rate (about one to three beats per minute on average) and higher levels of pancreatic enzymes like amylase and lipase, though it’s unclear if these changes have harmful effects. Gastrointestinal issues can also continue for some patients: In one study of patients taking tirzepatide for more than nine months (36 weeks), diarrhea (11%), nausea (8%), and vomiting (6%) were the most common long-term side effects. 

Other long-term side effects that can occur include “persistent GI intolerance or nutritional challenges, possible mood or behavioral changes, and weight regain upon stopping,” Dr. Tambini adds.

Zepbound interactions

Like many medications, Zepbound can interact with other drugs, changing how they work and increasing the risks of side effects:  

• People on other GLP-1 drugs such as Ozempic (semaglutide) or Saxenda (liraglutide) should not be prescribed Zepbound, as they have similar effects that can compound.
• People on insulin may need to work with their healthcare provider to reduce their dosage of insulin or insulin-affecting drugs (e.g., sulfonylurea drugs such as Glipizide). Otherwise, there may be an increased risk of hypoglycemia, or low blood sugar, which can cause dizziness, lightheadedness, weakness, or fainting.
• Zepbound can reduce the effectiveness of birth control pills (oral contraceptives). People on birth control pills may need to explore non-oral birth control methods, including barrier methods (condoms), contraceptive injections, patches, or intrauterine devices four weeks after starting or increasing Zepbound dosage. 
• Zepbound slows down how food and oral medications move through the digestive system. For this reason, it has the potential to affect how any oral medication is absorbed into the bloodstream. Healthcare providers may monitor people on drugs that require specific blood levels to work, such as warfarin, antidepressants, and antibiotics. 

Safety measures while using Zepbound

Zepbound isn’t safe for everyone. People with certain health conditions or risk factors may need to avoid it altogether, while others should use it with caution and close monitoring. 

Similar to Wegovy (semaglutide), Zepbound carries a black box warning of its risk of developing certain types of thyroid cancers. In clinical studies with rats, tirzepatide caused medullary thyroid cancer, thyroid C-cell tumors. The risk of tumor development increased with higher doses and longer treatments. The warning states that it’s not clear whether tirzepatide causes thyroid C-cell tumors in humans. Symptoms of thyroid cancer include swelling in your neck, trouble swallowing, hoarseness, or shortness of breath.

RELATED: Zepbound vs. Wegovy for weight loss

Zepbound may not be safe for the following populations:

• People with a history of medullary thyroid cancer (MTC) or multiple endocrine neoplasia syndrome type-2 (MEN-2) 
• Children, adolescents, and teens younger than 18 
• People who have an allergy to tirzepatide, other GLP-1s, or Zepbound’s inactive ingredients 
• People with Type 1 diabetes or latent autoimmune diabetes 

There’s not enough data on whether Zepbound is safe for pregnant or breastfeeding people. In addition, Zepbound’s drug label states that there’s no benefit to weight loss in a pregnant patient, and it may cause harm to the fetus. 

As stated previously, Zepbound can increase the risk of complications in people with certain conditions. People with diabetic retinopathy, on diabetes medication, undergoing general anesthesia, taking medications for high blood pressure, or who are at risk of dehydration require more caution and monitoring when taking Zepbound.

The highest dosage for Zepbound is 15 mg weekly. People who overdose on tirzepatide should contact 911 and poison control. The drug has a half-life of five days, meaning levels of the drug can still remain high for a few days before coming down to safe levels. 

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How to avoid Zepbound side effects

Not every side effect can be prevented, but there are steps you can take to lower your risk of certain symptoms. Here are some factors to consider to avoid Zepbound side effects:

1. Take Zepbound on the same day every week and never change your dosage without your healthcare provider’s supervision. If you miss your scheduled dosage day, take your next dose as soon as you remember, unless you’ve missed it by more than four days. In that case, wait for your next scheduled dose. 
2. Check each dose of Zepbound to make sure that it’s clear and colorless (or slightly yellow) before injecting.
3. Inject the medication in the abdomen, thigh, or upper arm, rotating injection sites with each dose. 
4. Use Zepbound along with a reduced-calorie diet and physical activity plan. Seek professional guidance from licensed nutritionists or dietitians and physical therapists to create a treatment that’s best for you. Consider training with weights to avoid muscle loss. 
5. “Zepbound has no direct food restrictions, but eating high-fat meals may worsen nausea and other GI side effects,” Dr. Tambini says. 

How to treat side effects of Zepbound

If side effects do show up, there are ways to manage them along with your healthcare provider’s guidance. “Most common side effects (GI issues, injection site issues) are treated with lifestyle adjustments, hydration, and sometimes over-the-counter medications,” Dr. Tambini says. 

Side effects of Zepbound can be treated with dietary changes. “For example, constipation can be relieved by increasing dietary fiber, and dehydration can be resolved by focusing on staying well-hydrated. Nausea and abdominal pain can be alleviated by eating small meals and avoiding fatty or ultraprocessed foods,” Dr. Brown shares. 

If you notice severe or prolonged side effects of Zepbound, it’s best to work with your healthcare team to manage symptoms and continue treatment safely. Abdominal pain is a common side effect of Zepbound, but it can be a sign of gallbladder or pancreatic inflammation, which could be a medical emergency. 

Bottom line

Zepbound carries a side effect profile similar to other drugs in the GLP-1 class—the most common being digestive symptoms like nausea, vomiting, and diarrhea. Your body may adapt to the medication or you may be able to manage side effects through lifestyle modifications or medical treatment. Zepbound also has serious side effects, such as risk of gallbladder or pancreatic inflammation, and carries a black box warning for thyroid C-cell tumors. 

RELATED: Zepbound alternatives

Because of its possible side effects, it’s important to always take Zepbound according to your healthcare provider’s instructions. If you experience any side effects, it’s worth contacting your medical team to make sure your treatment is safe and effective.