Obesity is a complex, chronic disease that affects nearly half of adults in the United States. Zepbound® is the most recently approved weight loss medication and boasts the highest average weight loss seen in clinical trials to date. While Zepbound offers promising benefits for weight loss, it is important to be aware of the potential side effects, which can range from mild to serious in nature. In this article, we will review both common and rare side effects of Zepbound for weight loss and how to minimize the risk of developing these side effects.

What is Zepbound used for?

Zepbound, which contains the active ingredient tirzepatide, is a once-weekly injectable medication that is used along with a healthy diet and exercise to aid in weight loss. In clinical trials, patients lost 26.6% of their body weight after a year and a half of taking tirzepatide combined with intensive lifestyle changes. Unlike other weight loss medications, it is the first single molecule that mimics two naturally occurring hormones in the body: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Zepbound activates both the GIP and GLP-1 receptors throughout the body, which improves insulin sensitivity, stimulates insulin release, slows down stomach emptying, and reduces food intake. The dual action of Zepbound on GIP and GLP-1 receptors produces a synergistic effect, which combined with lifestyle changes can lead to weight loss percentages only previously seen with weight loss surgery.

Common side effects of Zepbound

Although Zepbound is generally considered a safe and effective medication, it's important to acknowledge that like any medication, there are potential side effects that should be kept in mind. Some of the common side effects of Zepbound include, but are not limited to, nausea, diarrhea, decreased appetite, vomiting, constipation, indigestion, and stomach pain. Most gastrointestinal symptoms occur shortly after starting treatment or altering the dosage and typically go away after a few days or weeks as the body builds a tolerance to each dose. The SURMOUNT-3 clinical trial evaluated the safety of tirzepatide in adults with obesity or overweight. Mild to moderate gastrointestinal symptoms were the most commonly reported among patients in this study, specifically due to the increase in dosage of the medication. 

Serious side effects of zepbound

Although the majority of Zepbound’s side effects are mild and temporary, it's important to be aware of the existence of rare yet severe side effects that require consideration.

Zepbound has a boxed warning for the risk of medullary thyroid cancer. A boxed warning alerts healthcare providers and patients about the most serious side effects a drug may cause. Similar to GLP-1 medications, Zepbound caused thyroid tumors, including medullary thyroid cancer, in rodent studies. It is unknown whether Zepbound will cause thyroid tumors, or this type of thyroid cancer, medullary thyroid carcinoma (MTC), in humans. Due to this risk, Zepbound should not be used in patients with a personal or family history of MTC or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Other serious side effects of Zepbound include:

Pancreatitis: Indications of pancreas inflammation can include intense mid-upper abdominal pain, often extending to the back, along with feelings of intense and unrelenting nausea and vomiting. If you experience these symptoms while using Zepbound, discontinue the medication immediately and seek medical assistance.

Hypoglycemia: Low blood sugar can occur if Zepbound is used in combination with insulin or sulfonylureas (e.g., glyburide, glimepiride, glipizide), or other medications that can cause low blood sugar. Signs and symptoms of hypoglycemia may include dizziness, sweating, confusion, blurred vision, shakiness, fast heartbeat, irritability, hunger, weakness, and jitteriness. If you are taking Zepbound with other medications that can lead to low blood sugar, maintain regular monitoring of your blood sugar levels and schedule follow-up appointments with your healthcare provider for any necessary medication dose adjustments.

Serious allergic reaction: Symptoms of serious allergic reaction may include swelling of the lips, tongue, throat, or face, difficulty breathing or swallowing, severe rash or itching, and fainting or feeling lightheaded. Stop using Zepbound and seek medical attention right away.

Kidney injury: Severe diarrhea and vomiting can result in fluid loss, potentially affecting kidney function. Ensure you stay well-hydrated by consuming ample fluids while using Zepbound to prevent dehydration.

Changes in vision: Monitor for any vision changes during treatment with Zepbound. It is important to tell your healthcare provider if you experience changes in vision which can be related to how Zepbound impacts blood sugars

Gallbladder disease: Symptoms of gallbladder problems may include right upper abdominal pain, fever, yellowing of the skin or eyes, and clay-colored stools. Alert your healthcare provider right away if you develop these symptoms.

These side effects should be taken into account when deciding on a treatment strategy, as Zepbound may not be suitable for every individual. The decision to start a medication should be discussed with your healthcare provider. It is important to work with a medical weight loss program that understands your health history and goals in order to develop a treatment plan that is safe and effective for you.

How to minimize the risk of Zepbound side effects

Zepbound side effects will vary from person to person and can be affected by many factors, including medical history, medications, and lifestyle.

In order to minimize the risk of side effects, Zepbound is initiated at the lowest dosage of 2.5 mg per week. After a duration of 4 weeks, the dosage is raised to 5 mg. Additional dose increments may be made based on the individual's tolerance levels. Typically, the dosage is raised in 2.5 mg increments every 4 weeks, up to a maximum of 15 mg per week. If a particular dosage is not well tolerated, it may be advisable to remain at the current dosage for an extended period before considering further increases or potentially reducing the dose. Many of these side effects can be effectively managed through dietary and lifestyle adjustments.

For patients taking insulin or sulfonylureas, speak with your healthcare provider about reducing the dose of these medications to reduce the risk of hypoglycemia. Zepbound may potentially affect the absorption of oral medications so close monitoring is indicated. For patients taking oral contraceptives, use an additional form of birth control for 4 weeks after initiation and for 4 weeks after each dose escalation as Zepbound can decrease the effectiveness of oral contraceptives. 

Additionally, certain types of food can exacerbate some of Zepbound's side effects or hinder your efforts to achieve weight loss. You may want to consider certain foods to avoid on Zepbound as well as incorporating others which will help aid in your weight loss journey.

When should you see a doctor?

Although dietary and lifestyle modifications can often mitigate many of Zepbound’s side effects, patients should promptly consult a healthcare professional if they encounter any of the severe side effects mentioned earlier while using Zepbound. A healthcare provider can assist patients in addressing these potential side effects and determining the appropriate treatment plan. In the case of common gastrointestinal side effects, your doctor may have the option to prescribe anti-nausea medication or suggest over-the-counter remedies to aid in the management of these side effects.

Take control of your health: Mastering Zepbound side effects with confidence

As is the case with any medication, it is crucial to remain informed about the possible side effects associated with Zepbound, which can vary in severity from mild to potentially serious. These side effects often occur when starting or adjusting the dosage and usually become less problematic over time. It is advisable to use Zepbound under medical supervision to ensure its safety and suitability for your individual needs.

At Form Health, we conduct a thorough intake at your first appointment including your medical history and lab work to ensure that Zepbound is safe and appropriate for you. F patients have access to their dedicated Care Team via messaging in the F to ask any questions or share concerns about side effects. Our comprehensive approach includes personalized lifestyle and medical support to help you manage the potential side effects of Zepbound. If you are interested in learning whether Zepbound is a good option to help you achieve your weight loss and health goals,  send a message to Form Health to learn more. You can also take our quiz to find out if you are eligible. 

For more information, visit the Zepbound® product label and medication guide. 

Zepbound® and its delivery device bases are registered trademarks owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.

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Disclaimer: The content made available on The Form Health Medical Weight Loss Blog represents the views and opinions of the authors and not those of other entities, such as the manufacturers of products mentioned therein.