hands holding an injections drawing out a fluid from a vial

Zepbound Side Effects: Common, Serious, And How To Manage Them

Zepbound is an FDA-approved drug for the management of obesity. It may cause common side-effects such as nausea or vomiting; however, the more severe and long-term side-effects of Zepbound, like kidney failure and the risk of thyroid cancer, need to be considered before making an informed decision regarding its use.

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Lose weight with FDA-approved semaglutide weight loss injections (the same ingredient in Wegovy & Ozempic). If you are eligible, in-home medical weight loss treatments may help you reach your health goals.

The U.S. Food and Drug Administration approved Zepbound in May 2022 to manage obesity in adults. Zepbound contains the active ingredient tirzepatide, which activates GIP and GLP-1 receptors in the body.

Both GLP-1 and GIP are naturally occurring hormones that help reduce calorie intake and appetite.

When administered once a week alongside a reduced-calorie diet and increased physical activity, Zepbound has been shown to enhance the magnitude of weight loss efforts substantially.1

hands holding an injections drawing out a fluid from a vial

This medication may prove particularly useful for type 2 diabetes and chronic weight management for obese or overweight adults with at least one weight-related condition (e.g., HTN, T2DM, or high cholesterol.)

While Zepbound has the potential to be a breakthrough medication for obesity management, patients and healthcare providers alike should be aware of its potential side effects. Gaining insight into the possible side effects of Zepbound and learning how to manage them empowers individuals to make informed decisions for their health.

Who Should Not Use Zepbound?

Zepbound is a GLP-1 and GIP analog and is not recommended for use in patients on other drugs with similar mechanisms of action since these drugs can interact and cause undesirable effects.

Certain health conditions may put you at risk if you are taking Zepbound. These are known as contraindications. The absolute contraindications of Zepound usage are:

  1. Multiple endocrine neoplasia type 2 (MEN 2): If you have a history or are presently battling MEN 2, Zepbound is not appropriate for you. MEN 2 is a condition that puts a patient at risk for thyroid cancer. Since Zepbound comes with a boxed warning for the risk of thyroid cancer, Zepbound puts patients with MEN 2 at an increased risk of developing thyroid cancer.
  2. Medullary thyroid carcinoma (MTC): If you or a family relative has a history of MTC, Zepbound can increase the risk of thyroid cancer.
  3. Zepbound Allergies: This is a frequent contraindication for many drugs. If you develop an allergic reaction to Zepbound or have an existing allergy to any of its ingredients, you cannot be prescribed the medication.

Prevalent Side Effects of Zepbound

The most commonly reported side effects associated with Zepbound use are nausea and diarrhea, which may occur in up to 10% of patients. Vomiting and acid reflux have also been infrequently reported. However, nausea is a symptom that may be improved with continued use of Zepbound.

The other side effects of Zepbound occur locally at the injection site. These may include:

  • Rash
  • Swelling
  • Pain
  • Bruising

These reactions can typically be avoided by providing training for patients and caregivers on proper injection techniques.

Serious Side Effects and Health Concerns

While most patients tolerate Zepbound well, some may experience severe responses that require immediate medical attention. These adverse reactions include:

Kidney Problems and Dehydration

Zepbound can increase the risk of dehydration, especially in patients with preexisting kidney problems or those currently taking diuretic medications.

Dehydration may present clinically as:

  • Excessive thirst
  • Dry mouth
  • Dark/concentrated urine
  • Fatigue
  • Dizziness
  • Decreased urine output

Patients should maintain adequate hydration by drinking plenty of fluids, particularly water, and avoiding excessive alcohol consumption when using Zepbound. Healthcare providers may monitor kidney function through regular blood tests and adjust medication dosages as needed.

Gallbladder Issues

Zepbound may increase the risk of gallbladder-related complications, including gallstones and cholecystitis (inflammation of the gallbladder). It is critical to report symptoms such as nausea, jaundice, or severe abdominal pain and to seek medical attention as soon as possible.

Thyroid C-Cell Tumors

In rare cases, Zepbound may stimulate the growth of thyroid C-cells, leading to the development of tumors known as medullary thyroid carcinoma (MTC). As mentioned previously, patients with a personal or family history of MTC or MEN 2 should not use Zepbound due to this risk.

Severe Allergic Reactions

If you are allergic to Zepbound or any of its active ingredients, you may have an allergic reaction to it.

Allergic reactions can vary from moderate to severe and may manifest themselves as: 

  • Swelling of face, lips, throat, or tongue
  • Breathing complications
  • Rash
  • Itching

Serious allergic reactions, known as anaphylaxis, require emergency medical treatment.

Does Zepbound Cause Depression?

recent study showed that some specific weight loss medications, such as tirzepatide, might reduce their chances of being diagnosed with depression when compared to those who are not using a GLP-1 medication.2

However, the FDA has received reports on suicidal thoughts or actions in patients taking certain GLP-1 agonists, including tirzepatide. Their preliminary evaluation has not found any conclusive evidence linking the drugs to suicidal thoughts; however, a detailed review is still pending.

Patients need to communicate any disruptions in relation to mood or behavior to their healthcare providers for further evaluation and management.

Zepbound’s Impact on Kidney Function

Given the potential for Zepbound to affect kidney function, regular monitoring of renal parameters is essential for patients on this medication. Healthcare providers may conduct periodic blood tests such as blood urea nitrogen and creatinine levels to assess kidney function and adjust treatment accordingly. Patients should also maintain adequate hydration and promptly report any signs of dehydration or kidney problems to their healthcare provider.

Managing and Reducing Zepbound Side Effects

There are several measures you can take to manage and reduce the side effects of Zepbound.

  • Dietary Adjustments: Making effective modifications to your diet can help alleviate the gastrointestinal side effects of Zepbound. A diet rich in fiber, fruits, and vegetables can help with symptoms such as nausea and diarrhea. Patients should also avoid spicy, greasy, or heavy meals that may exacerbate digestive discomfort and may also be helpful for lessening the risk of developing gallbladder issues.
  • Proper Injection Techniques: As discussed previously, inadequate injection procedures can cause site reactions such as pain, redness, and swelling. It is important to give sufficient training for injection techniques to both patients and their caregivers.
  • Staying Hydrated: Patients should maintain adequate hydration to prevent dehydration and reduce the risk of kidney problems associated with Zepbound use. Patients should aim to drink at least eight glasses of water daily while avoiding excessive consumption of caffeinated or alcoholic beverages. Additionally, your hydration needs must be increased if you have diarrhea, nausea, and vomiting, as they cause a loss of fluids, too.


Zepbound (Tirzepatide) is a medication that has recently been approved for chronic management of obesity. While it offers therapeutic benefits, patients should be conscious of its potential side effects, ranging from mild gastrointestinal symptoms to serious health concerns such as kidney problems, pancreatitis, and a boxed warning for thyroid cancer.

By understanding these side effects and implementing effective management strategies, patients can optimize their treatment outcomes and maintain their overall well-being. It’s essential to communicate any concerns or adverse reactions to healthcare providers promptly for appropriate evaluation and intervention.

Reach Your Weight Loss Goals With Semaglutide

Semaglutide (the same ingredient in Wegovy and Ozempic) is the only proven FDA-approved medication for long-term weight loss and management. Medical weight loss medications can help you on your journey toward your ideal weight.

Book a convenient online consultation and health check followed by a lab test. Eligible individuals will receive a medical weight loss prescription with medications delivered directly to your home.

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[1] Wadden TA, Chao AM, Machineni S, Kushner R, Ard J, Srivastava G, Halpern B, Zhang S, Chen J, Bunck MC, Ahmad NN, Forrester T. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nat Med. 2023 Nov;29(11):2909-2918. doi: 10.1038/s41591-023-02597-w. Epub 2023 Oct 15. Erratum in: Nat Med. 2024 Feb 27;: PMID: 37840095; PMCID: PMC10667099.;

[2] Miller A, Joyce B, Bartelt K, Deckert J. Most GLP-1 Medications Correlated with a Lower Likelihood of Anxiety and Depression Diagnoses. Epic Research. https://epicresearch.org/articles/most-glp-1-medications-correlated-with-a-lower-likelihood-of-anxiety-and-depression-diagnoses. Accessed on April 15, 2024.;