Zepbound Side Effects

It's not a given that you'll experience Zepbound side effects, but it's helpful to know what could happen before you start treatment. With that information, you’ll feel more prepared and will know what to mention to your provider during your check-ups. Here's a guide to potential Zepbound side effects and what you can do to feel your best while taking the medication.

What is Zepbound?

Zepbound, a brand name of the drug tirzepatide, is a GLP-1 medication that mimics two hormones: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These hormones play a major role in stimulating the pancreas to release insulin — which helps keep blood sugar regulated — as well as suppressing the appetite and prompting feelings of fullness.

Zepbound was approved by the FDA in November 2023 for chronic weight management in adults with obesity as well as those who are overweight and have at least one weight-related condition like high blood pressure or high cholesterol. (A different version of tirzepatide, Mounjaro, was approved by the FDA in May 2022 for type 2 diabetes management in adults, as a way to improve blood sugar when combined with diet and exercise.)

In December 2024, Zepbound was also approved for the treatment of moderate to severe obstructive sleep apnea in adults with obesity. And while the medication is not currently FDA-approved to treat heart disease, clinical trials suggest it may help.

Common side effects of Zepbound

The most common of Zepbound’s side effects tend to be disruptive but relatively mild. They include:

• Nausea
• Constipation
• Diarrhea
• Indigestion
• Vomiting

"Common side effects like these tend to happen most when you first start Zepbound, or when you're increasing your dosage," says Dr. Sue Decotiis, M.D., a triple board-certified physician in internal medicine, antiaging medicine, and obesity medicine, who leads a weight-loss practice in Scarsdale, NY. "That means you may have an effect like nausea or constipation for a few days, and then it will lessen or go away as your body gets used to the medication." Find a full list of Zepbound side effects on the Zepbound site.

Mild side effects of Zepbound

In addition to the gastrointestinal issues that are the most common, most of the other reported side effects of Zepbound are mild and often temporary, says Decotiis. Those include:

• Abdominal pain, such as tenderness and cramping
• Burping
• Dizziness
• Fatigue
• Gassiness
• Hair loss
• Injection site reactions

"These types of effects can be uncomfortable at the time, but they're not usually enough to change your Zepbound dosage or switch to a different medication, especially since they are often alleviated by staying on Zepbound for a few weeks or longer,” Decotiis says. “However, if they're worsening or are impacting your everyday life, you should talk with your health care provider about different strategies, such as waiting a longer amount of time to increase your dosage."

Serious side effects of Zepbound

According to the FDA, some serious health issues occurred in clinical trials of people taking tirzepatide, including:

• Severe allergic reactions
• Pancreatitis (inflammation of the pancreas)
• Hypoglycemia (low blood sugar)
• Severe digestive problems, which could lead to acute kidney injury
• Gallbladder problems
• Medullary thyroid cancer

The FDA also notes that there’s insufficient data about use of tirzepatide in pregnant women when it comes to risk of birth defects and miscarriage, but there is some evidence in animal studies that a fetus could be affected during pregnancy. Because of that, a Zepbound prescription is not recommended for use during pregnancy.

Explanation of Zepbound side effects

In terms of why Zepbound may cause side effects, it’s because it takes the body time to adjust to the medication, especially when you first start taking them, according to Dr. Alexandra Sowa, M.D., a New York City-based physician double-board certified in internal medicine and obesity medicine, and the author of The Ozempic Revolution. For example, Zepbound can slow gastric emptying — meaning food sits in your stomach longer — which may prompt nausea initially, until your body adjusts to that slower digestion timeframe. Here’s a deeper dive into some of the other side effects.

Medullary thyroid cancer risk

There's an FDA warning about avoiding tirzepatide if you have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasias because the medication may increase your risk of developing thyroid cancer. That's based on research involving rats, however, and no studies done on humans have established the same connection. That said, doctors do still want people taking tirzepatide to know about this risk, as well as the signs of thyroid cancer.

Tips for identifying thyroid cancer

Thyroid cancer can cause any of the following symptoms:

• Lump in the front and/or side of the neck
• Swelling and/or pain in the neck
• Hoarseness or other voice changes that don't go away
• Difficulty breathing
• Trouble swallowing
• Constant cough not related to a cold or other recent illness

Keep in mind that many of these symptoms can also be caused by non-cancerous conditions, and that lumps in the thyroid are common. But if you have any of these symptoms, it's essential to see your doctor to get assessed for possible thyroid cancer.

Stomach pain and indigestion

Because of slower gastric emptying, Zepbound may lead to stomach pain that feels like cramping or tenderness, says Sowa. You might also experience abdominal pain due to digestion issues such as constipation, bloating, or gas.

Tips for managing stomach problems and indigestion

Here are some strategies to alleviate both stomach pain and indigestion when taking Zepbound:

• Eat smaller meals throughout the day and try to slow down how fast you eat, since that can help reduce bloating and discomfort.
• Avoid using a straw when drinking, which will lower how much air goes into your stomach (a cause of bloating).
• Limit or avoid fatty, fried, spicy, and sugary foods, since these can irritate the stomach lining.
• Gradually increase fiber intake with fruits, vegetables, and whole grains, rather than significantly boosting fiber all at once (something that can lead to bloating and gas).
• Take a leisurely walk after eating to aid in digestion, but avoid strenuous exercise, since that may worsen symptoms.
• Stay hydrated, since water can help move food through your system more efficiently.
• Avoid eating too close to bedtime, since that can make indigestion more likely.

As with any Zepbound side effects, if your stomach problems or indigestion get worse, Decotiis says to talk with your health provider and work on a solution.

Injection site reactions

Because Zepbound is given as an injection (vial or Zepbound pen), you may notice redness, itchiness, or a painful sensation around the site, which can last for a few hours but may linger for a couple days in some instances, according to Sowa. If you have a more serious allergic reaction — such as hives, swollen or blistering skin, or itching that keeps getting worse — reach out to your health provider immediately as these can be signs of a serious allergic reaction.

Tips for managing injection site reactions

Similar to other diabetes and weight-loss medications that use injections, site reactions tend to occur more commonly if you're doing the injections at the same place on your body each time, says Sowa. Because of that, experts recommend you rotate injection sites each time. For example, if you prefer to use your stomach for injection, alternate which side of the abdomen you inject into each time. Also, try to avoid injecting within two inches of the belly button or too close to the hipbones, since this can increase your likelihood of pain and tenderness, Sowa adds. Another tip: Inspect your injection site first to ensure the skin looks healthy. Injecting into skin that's bruised, scraped, scaly, dry, or tender may increase your risk of an injection site reaction.

The bottom line

By bringing together two different hormones, GLP-1 and GIP, Zepbound has been shown to be effective in helping with weight loss and weight management. As with any medication, it's important to know about potential side effects before you begin treatment. The most common Zepbound side effects tend to be nausea, constipation, diarrhea, indigestion, and vomiting, but you may also experience other mild and, in rare cases, more severe side effects. Make sure to talk with your health care provider about any side effects and to learn what strategies may help you feel better.