Zepbound side effects: what to expect and how to reduce them

Yael Cooperman, MD - Contributor Avatar

Reviewed by Yael Cooperman, MD, Ro, 

Yael Cooperman, MD - Contributor Avatar

Reviewed by Yael Cooperman, MD, Ro, 

LAST UPDATED: Jan 08, 2024

7 MIN READ

Zepbound is a medication used along with diet and exercise to promote weight loss in people with obesity or weight-related health problems. It’s the latest addition to a popular group of medications that also includes Mounjaro and Ozempic

If you recently started using Zepbound and feel sick to your stomach, you’re not alone. The most common complaints with Zepbound are nausea and other stomach problems. The good news is these side effects usually go away with time as your body gets used to the medication. 

Keep reading to learn more about the common side effects of Zepbound and tips on dealing with them, as well as what to know about other potential side effects of the medication.

Zepbound Important Safety Information: Read more about serious warnings and safety info.

Mounjaro Important Safety Information: Read more about serious warnings and safety info.

Ozempic Important Safety Information: Read more about serious warnings and safety info.

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What is Zepbound?

In 2023, the Food and Drug Administration (FDA) approved Zepbound for weight management. The active ingredient, tirzepatide, was already available as Mounjaro, a brand-name medication prescribed to treat type 2 diabetes. 

More specifically, Zepbound is FDA-approved to be used alongside a reduced-calorie diet and increased exercise for chronic (long-term) weight management in certain people, including:

  • Adults with obesity, defined as an initial body mass index (BMI) of greater than or equal to 30 kg/m2, or

  • Adults with an initial BMI of greater than or equal to 27 kg/m2, along with at least one weight-related health condition such as high blood pressure, obstructive sleep apnea, or type 2 diabetes

Zepbound comes in a prefilled, single-dose pen that patients use to inject themselves and is available in six dosage strengths: 2.5 milligrams (mg), 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg. Unlike Ozempic, which targets just GLP-1 receptors, Zepbound has dual action, stimulating both GLP-1 receptors and GIP receptors, giving it unique properties when it comes to helping with weight management. Tirzepatide increases insulin production and slows the digestion process. Increased insulin helps lower blood sugar levels, while slower digestion leads to increased satiety (feeling “full”) and reduced food intake, resulting in patients shedding significant weight.

What are the common side effects of Zepbound? 

Zepbound may cause side effects in some people. The most common side effects of Zepbound are usually related to the digestive system and can include nausea, vomiting, diarrhea, and constipation. Clinical trials have shown that these symptoms are typically most bothersome for patients right after dosage increases but tend to subside with continued use. 

In clinical trials for Zepbound, researchers determined these possible side effects by comparing the drug to a placebo. A placebo is an inactive medication used as a comparison for a drug product in studies. The placebo is usually designed to look similar and is administered the same way as the drug. Typically, these trials are “double-blinded,” meaning that the trial participants and clinicians do not know who is receiving the drug versus the placebo. The FDA reviews this data to decide if the medication is reasonably safe. This chart shows how often patients in one Zepbound trial reported side effects. You can see that the most common side effects were digestive in nature:

Side Effect

Placebo

Zepbound*

Nausea

8%

25–29%

Vomiting

2%

8–13%

Diarrhea

8%

19–23%

Constipation

5%

11–17%

Injection site reactions

2%

6–8%

Fatigue

2%

5–7%

Hair loss

1%

4–5%

Stomach upset 

4%

9–10%

*Side effects reported across dosage range of 5 milligrams (mg), 10 mg, or 15 mg once weekly.

How can I reduce Zepbound side effects? 

For some people, the side effects of Zepbound can be quite uncomfortable. Let’s look at the details of Zepbound’s common side effects and offer tips on how to manage them.

Nausea, vomiting, and upset stomach

Nausea is the most common side effect of Zepbound. Vomiting and upset stomach (e.g., bloating, heartburn, reflux, abdominal pain, belching, passing gas) are also common.  

When starting Zepbound treatment or increasing the dose, these side effects are usually more frequent or bothersome. Most people notice a gradual decline in the frequency and severity of nausea and vomiting side effects the longer they take Zepbound. 

The nausea side effect is the main reason your healthcare provider will prescribe a low dose of Zepbound to start. The initial dose is 2.5 milligrams (mg), which is well below the recommended target dose that promotes weight loss. However, starting with a low dose helps the body adjust to the medication. Your provider will have you slowly step up your dose every four weeks or so until you reach either the target dose or the maximum dose you can tolerate. This gradual approach helps ensure your body adjusts to tolerating the drug. So, it’s essential to follow your provider’s instructions.

Making a few small dietary changes can be really helpful strategies to help minimize nausea, vomiting, and other stomach side effects while using Zepbound, such as: 

  • Eating smaller meals. Similar to other GLP-1 medications for weight loss, Zepbound slows digestion and keeps food in the stomach for longer. This results in a faster and longer-lasting feeling of fullness. However, if you continue to eat despite feeling full, this may lead to nausea and vomiting. It’s best to opt for smaller portion sizes and stop eating once you feel full. This strategy not only increases the weight loss potential of the medication but helps reduce uncomfortable side effects. 

  • Choosing foods carefully. Certain foods may worsen the digestion-related side effects of Zepbound, like high-fat and spicy foods. Avoiding these foods may reduce the chance of experiencing nausea or vomiting with Zepbound. However, foods that result in nausea or vomiting may vary depending on the individual. For this reason, it’s a good idea to pay attention and keep track of which foods may trigger these side effects, then come up with a meal plan that avoids triggers. Similarly, heavy alcohol consumption can be a potential driver of these side effects. Because of this, healthcare providers recommended avoiding or limiting alcohol intake while using Zepbound or other GLP-1 medications.

Over-the-counter (OTC) medicines may also provide temporary relief, depending on your symptoms. For instance, antacids like Tums work to ease heartburn, and simethicone (brand name Gas-X) can help with bloating and gas. Consult a pharmacist if you’d like help choosing an OTC medication.

Diarrhea

Diarrhea is a common side effect of Zepbound. This side effect occurs more frequently when treatment first starts and after dose increases. As with nausea, diarrhea typically decreases as the body adjusts to Zepbound. 

Your healthcare provider will gradually increase your dose over several months until you reach the target or maximum dose. This helps your body adjust to the drug. Be sure to follow your provider's instructions and not increase the dose too quickly.

Some tips to assist in avoiding or lessening diarrhea with Zepbound include:

  • Watching dietary fat intake. High-fat foods can be more challenging for the body to digest, especially when adjusting to Zepbound, and may result in diarrhea. 

  • Following the BRAT diet. Eating bland foods, like basic rice or toast, may help reduce stomach upset leading to diarrhea. 

Additionally, be sure to drink plenty of fluids to combat dehydration that can result from diarrhea. 

Constipation

It is common to experience constipation while taking Zepbound. This side effect can be attributed to the drug’s mechanism of action; since Zepbound slows stomach emptying (part of digestion), food takes longer to move through the digestive tract. In some instances, this results in constipation or hard stools.

Remember that Zepbound is meant to be used in conjunction with increased physical activity. Exercise can help relieve constipation.

Other methods that can help reduce or prevent constipation include: 

  • Modifying your diet: Fiber is an essential component of the diet. It aids in bowel regularity by increasing the bulk of the stool and making it softer; both of these factors help make stool easier to pass. Focusing on eating high-fiber foods helps combat constipation by bulking up the stool despite the fact that you may be eating less than before you started the medication. Some key foods with high fiber content include fresh fruits, vegetables, and grains.

  • Increasing hydration. When you don't drink enough fluids, you can get constipated. And if you're taking Zepbound, which slows digestion, it's even more likely that you'll have constipation if you’re not drinking much water. So, drinking a lot of water throughout the day can promote normal bowel function and assist in keeping things moving.

  • Using OTC medications. In some instances, lifestyle changes aren’t enough. OTC laxatives or stool softeners may help. For example, Miralax is a gentle laxative that helps increase the amount of water in stool, softening it and promoting bowel movements. Additionally, OTC fiber supplements, such as Metamucil, are an easy way to increase fiber intake to support healthy bowel function.

Injection site reactions

Zepbound is given by subcutaneous injection once weekly. This injection goes under the skin of the abdomen, thigh, or upper arm. As a result, injection site reactions may occur, such as pain, irritation, bruising, redness, itching, or rash. 

To help avoid these reactions, your healthcare provider will show you how to inject Zepbound using the proper technique. If injection site reactions occur, reach out to your healthcare professional for assistance. They can demonstrate or observe your technique and provide feedback for more comfortable administration. 

Additionally, injecting cold medication can be more irritating. Store Zepbound in a refrigerator until 30 minutes prior to use. Taking the medication out of the refrigerator a half-hour ahead of time allows it to reach room temperature, which may reduce the likelihood of injection site reactions. (However, don’t expose the drug to direct sunlight or use any type of method to heat it up. This can ruin the medication).

Hair loss

Hair thinning or hair loss may occur while using Zepbound. Hair loss has also been observed in clinical trials for other GLP-1 drugs, as well.

Hair loss may occur as a result of rapid weight loss rather than the medication itself. If Zepbound is used for managing weight in obese or overweight individuals as intended, it is unlikely to cause significant hair loss. However, hair loss may occur and can even be permanent if drugs like Zepbound or Ozempic are misused, if weight is lost too quickly, or if a non-overweight or underweight person takes the drug.

If you experience hair loss when using Zepbound, speak with your prescribing doctor. They can perform a blood test to ensure that you don’t have any nutrient deficiencies, as well as adjust your dosing schedule if appropriate to slow the rate of weight loss. In addition, they can determine if you might have a different underlying condition that could be contributing to changes in your hair, such as thyroid disease

When should you stop Zepbound? 

In some instances, Zepbound may cause side effects that don’t go away on their own. If this occurs, reach out to a healthcare professional to discuss your next steps and options. They may advise you to decrease your dose, or restart you on a lower dose and increase the dose more slowly than before. In other cases, they may direct you to stop taking the medication. 

Rarely, serious side effects may occur during Zepbound treatment. Some symptoms may be a warning sign of serious side effects. Seek medical care right away if you experience:

  • Severe abdominal pain lasting longer than 24 hours, which may be a sign of pancreatitis or gallbladder disease

  • Swelling, difficulty breathing, or rash, which may be a sign of a severe allergic reaction

  • Dizziness, sweatiness, or blurred vision, which may be a sign of dangerously low blood sugar, especially if you take Zepbound in addition to certain diabetes medications, such as insulin or a sulfonylurea drug like glyburide

  • Vision changes, particularly if you have type 2 diabetes mellitus

  • Swelling or a lump in your neck, trouble swallowing, hoarseness, or shortness of breath. These may be symptoms of thyroid cancer. Zepbound carries a boxed warning for this risk. 

For more information about precautions and who should avoid Zepbound, talk with a healthcare provider.

The bottom line

Nausea, diarrhea, vomiting, and other side effects can occur while taking Zepbound. With time, most people report that nausea and vomiting happen less often and aren't as bad. Keep in mind that not everyone experiences side effects from Zepbound, and if they occur, they are likely to be mild or manageable.

Note that this article does not discuss all possible side effects of Zepbound. Speak with a healthcare professional to determine if this medication is appropriate for you.

DISCLAIMER

If you have any medical questions or concerns, please talk to your healthcare provider. The articles on Health Guide are underpinned by peer-reviewed research and information drawn from medical societies and governmental agencies. However, they are not a substitute for professional medical advice, diagnosis, or treatment.


How we reviewed this article

Every article on Health Guide goes through rigorous fact-checking by our team of medical reviewers. Our reviewers are trained medical professionals who ensure each article contains the most up-to-date information, and that medical details have been correctly interpreted by the writer.

Current version

January 08, 2024

Written by

Patricia Weiser, PharmD

Fact checked by

Yael Cooperman, MD


About the medical reviewer

Yael Cooperman is a physician and works as a Senior Manager, Medical Content & Education at Ro.

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