Tirzepatide side effects and risks: what to expect

Like any medication, tirzepatide — the active ingredient in Mounjaro and Zepbound — comes with a risk of side effects, the most common being gastrointestinal symptoms like nausea and constipation. However, more serious adverse effects are possible, too. Read on to learn more about the potential side effects and risks of this blood sugar control and weight loss medication.

Tirzepatide comes with a long list of potential side effects. Like all medications, some of these side effects are more common than others. The most common side effects shown in clinical trials involved mild to moderate gastrointestinal problems. 

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Reported side effects of tirzepatide

The active ingredient (tirzepatide) and dosing are identical in Mounjaro and Zepbound, which means their potential side effects are identical. The FDA labels have slightly different lists of side effects for each branded drug, though, since the clinical trials were done on different patient populations. 

Their shared common side effects include: 

• Nausea

• Diarrhea

• Vomiting

• Constipation

• Abdominal pain

• Dyspepsia (indigestion)

Mounjaro side effects

The only common side effect Mounjaro includes on its label that Zepbound doesn’t is decreased appetite. This isn’t listed as a side effect on Zepbound’s label since decreased appetite is one of the intended effects of the weight loss drug. 

Zepbound side effects

Clinical trials on Zepbound were done on a different patient population than Mounjaro, and several additional side effects happened in over 5% of trial participants (these side effects occurred in Mounjaro, too, just below the 5% threshold to be considered common).

• Fatigue

• Injection site reactions

• Belching (aka “sulfur burps”)

• Hair loss

• Gastroesophageal reflux disease (GERD)

• Hypersensitivity reactions

GI side effects are generally manageable and tend to improve the longer you are on the medication. Clinical trial participants reported the most discomfort when they first started taking tirzepatide, or when they increased their dose.

Work with your provider to find strategies to manage common side effects. This might include starting at the lowest dose and slowly increasing it, eating smaller meals, avoiding certain foods, and taking other medications to help minimize symptoms of nausea. 

While most people experience at least one side effect when being treated with glucagon-like peptide-1 receptor agonists (aka GLP-1s), tirzepatide seems to cause fewer adverse events than other drugs in this class, says  Christopher McGowan, MD, an obesity medicine specialist. 

“The overall rate of digestive side effects was lower with tirzepatide than with semaglutide in their respective trials, which is precisely what we see in clinical practice,” he explains. That may be because it acts on GIP receptors, not just GLP-1. 

Still, the risk of side effects remains. To mitigate these effects, Dr. McGowan recommends the following:

• Start at the lowest dose and then increase slowly based on the manufacturer’s recommendations. Starting at higher doses or skipping doses can lead to more severe side effects. 

• Ask your provider about taking an anti-nausea medication like ondansetron (Zofran) to settle your stomach.

• Stay hydrated by drinking plenty of water throughout the day.

• Eat smaller, more frequent meals to help mitigate indigestion or bloating.

• Avoid certain foods that could exacerbate GI side effects, such as greasy foods and carbonated beverages.

Most importantly, stay in contact with your provider. If your side effects are severe — or even if they’re mild but negatively impact your quality of life — communicate these issues right away. You don’t have to just power through discomfort. 

“Patients cannot be expected to manage side effects alone, so it is critical to communicate any symptoms to one’s treatment team,” says Dr. McGowan. Decreasing a dose or staying on one dose for longer may be needed. “Over time, most symptoms will improve as the body adapts to the medication,” he says.

More serious side effects can occur with both Mounjaro and Zepbound, though these are far less likely. Below is a breakdown of rare but serious warnings and precautions to consider with tirzepatide. 

If you experience any of the below side effects, stop taking the medication and talk to your healthcare provider about alternative options.

Serious hypersensitivity reactions and allergies

Although a mild rash and itching at the injection site are common reactions, more serious issues like hives and eczema are possible. 

While very rare, a life-threatening allergic reaction (anaphylaxis) has also been reported. This occurred in 0.1% of Zepbound patients and it has also been seen in patients taking Mounjaro. Always discuss any known allergies with your provider before starting a new medication. 

Other skin reactions, such as a condition called allodynia, have been reported as well, but this is an emerging area of research. 

Pancreatitis

Sudden inflammation of the pancreas (an organ that helps with digestion and blood sugar regulation) can occur, although it is rare and was only reported in 13 patients taking tirzepatide in clinical trials. 

Thyroid C-cell tumors

An increased risk of this specific type of cancer has only been seen in rodent studies, not in humans. Still, it’s listed as a warning for both Zepbound and Mounjaro. If you have a family history of these types of tumors, you shouldn’t take tirzepatide. 

Acute gallbladder disease

In trials for Mounjaro, 0.6% of participants reported gallbladder disease — including gallstones, gallbladder inflammation, biliary colic (intermittent or constant abdominal pain), and cholecystectomy (surgical removal of the gallbladder) — compared to no reports in the placebo group. 

Acute kidney injury

Kidney damage occurred in 0.5% of people on Zepbound versus 0.2% in those on placebo. These injuries are most likely caused by dehydration from GI side effects like nausea, diarrhea, and vomiting. It’s important to stay hydrated when taking this medication.

Vision changes

People with diabetic retinopathy (a complication of diabetes that leads to vision loss) may find that their symptoms get worse while taking tirzepatide. This is temporary, but contact your provider if you experience blurry vision, dark spots, or floaters while taking this medication. 

Increased heart rate

Some Mounjaro trial participants experienced an average increased heart rate of two to four beats per minute, compared to one beat per minute in the placebo group. It’s not clear what causes this or if it has any practical implications for treatment with tirzepatide. 

Here are the most important things to know about tirzepatide’s potential side effects:

• The most common side effects of tirzepatide include nausea, vomiting, diarrhea, and constipation.

• Rare but serious side effects include pancreatitis, diabetic retinopathy, specific kinds of thyroid tumors, and kidney injury. 

It’s important to be open with your prescriber about all potential health risks before you start any new medication, including tirzepatide. Tell them about any medications and supplements you currently take, your complete health history, and your family health history. This will help you and your provider better weigh your personal risks and benefits, and if tirzepatide is a good option for you. 

If you experience the following symptoms or side effects, you should stop taking tirzepatide and seek medical attention right away:

• Severe stomach pain that won’t go away

• Signs of an allergic reaction like problems breathing, feeling dizzy, or swelling of your face

• Symptoms of low blood sugar like dizziness, lightheadedness, confusion, fast heart rate, or increased anxiety

• Vision changes such as blurred vision, floaters, or black spots in your vision

• Signs of kidney injury, such as infrequent urination or swelling in your ankles, feet, or hands

• A lump in your neck, a hoarse voice that does not go away, trouble swallowing, or shortness of breath, which may be signs of thyroid tumors

Because tirzepatide slows stomach emptying, it may also affect how other medications get absorbed, which could interfere with their effectiveness. That’s why it’s important to always go over the list of medications and supplements you’re currently taking with your provider or a licensed pharmacist before starting tirzepatide. 

Talk to your provider if you are currently taking these medications: 

• Hormonal contraception: Tirzepatide may interfere with the effectiveness of oral hormonal birth control (the pill). Your provider might recommend switching to a different contraceptive method, such as non-oral birth control, or suggest using barrier methods (such as condoms) after starting or increasing your dose. 

• Diabetes treatment medications like insulin: Insulin and some oral diabetes medications, such as sulfonylureas, can increase your risk for hypoglycemia when used with tirzepatide, since tirzepatide also affects blood sugar levels. If your provider determines that you are a good candidate for tirzepatide, they may adjust the dosage of your diabetes medication. 

You should also avoid taking tirzepatide in combination with other GLP-1 receptor agonist medications. There is no evidence that taking two of these medications together is more effective for weight loss or blood sugar control, while combining them can increase your risk of severe side effects. 

Lastly, make sure your provider knows that you’re taking tirzepatide before you undergo any surgeries or procedures that require sedation.

There have been some reports of pulmonary aspiration (a complication where food from your stomach is inhaled into your lungs) while under general anesthesia or deep sedation in people taking tirzepatide, likely due to delayed stomach emptying. In this case, your provider may recommend a different fasting schedule to prepare for surgery. 

If you are pregnant or plan to become pregnant, you should not use tirzepatide. If you are breastfeeding, talk with your provider to determine if the benefits of tirzepatide outweigh the potential risks. 

If you have a personal or family history of certain health conditions, your provider may recommend a different medication, or they may want to watch you more closely for certain side effects and reactions. 

Tell your provider if you or your family members have a current or past history of:

• Diabetic retinopathy

• Pancreas or kidney problems, such as a history of pancreatitis

• Medullary thyroid cancer or Multiple Endocrine Neoplasia syndrome type 2 

• Severe gastrointestinal disease like gastroparesis (delayed gastric emptying that causes nausea, vomiting, or bloating)

• Serious allergic reaction to tirzepatide, including anaphylaxis

Tirzepatide is designed to be used alongside a reduced-calorie diet and regular exercise. Together, these help you get the most significant benefits for both weight loss and blood sugar control. 

Because tirzepatide reduces appetite and slows digestion, most people eat fewer and smaller meals while taking it. As a result, it’s important to eat a balanced diet to ensure you’re getting the nourishment you need. 

Aim for a diet that includes lots of vegetables, fruit, whole grains, legumes, lean proteins, and healthy fats to ensure you get essential nutrients. 

Many of these foods are also rich in fiber, which can help with bowel regularity — an important benefit when taking a GLP-1, says Charlie Seltzer, MD, a board-certified obesity medicine doctor in Philadelphia. He also recommends eating smaller, more frequent meals to help mitigate GI discomfort. 

Monitor your blood sugar levels and watch for signs of low blood sugar, such as confusion, fatigue, shaking, and heart palpitations. If you have type 2 diabetes, you should always carry a quick source of sugar like fruit juice, candy, or glucose tablets with you in case of a hypoglycemic episode.

Start your journey

When combined with lifestyle interventions like a reduced-calorie diet and regular exercise, both Zepbound and Mounjaro are effective at promoting weight loss and blood sugar control. While both medications are approved by the US Food and Drug Administration (FDA) and considered safe, they do come with the potential for mild side effects and serious health risks for certain people. 

• Tirzepatide works by mimicking two naturally occurring hormones (GLP-1 and GIP) that help to reduce blood sugar, suppress hunger cues, and slow digestion. 

• The most common side effects of tirzepatide are nausea, vomiting, constipation, and diarrhea. Side effects tend to go away the longer you are on tirzepatide, but they may flare up anytime you increase your dose. 

• Staying hydrated, taking anti-nausea medications, and slowly increasing your dose over time can help you manage side effects. 

• Serious side effects may include pancreatitis, kidney injury, allergic reactions, and vision changes, although these are rare. 

• Talk to your provider about all potential health risks before you start any new medication, including tirzepatide. This discussion should include any medications, supplements, and herbs you currently take, your complete health history, your family health history, and your weight loss goals.