Does Zepbound cause diarrhea?

Yes, Zepbound (tirzepatide) may cause diarrhea, one of the most common side effects reported when starting this medication. 

Maybe you saw it listed as a possible side effect, your healthcare provider mentioned it, or you're already dealing with it firsthand; regardless of what brought you here, know it's a common concern. Keep reading to learn how common Zepbound diarrhea is, why it happens, how to treat it, and when to speak with a healthcare provider.

Yes, Zepbound can cause diarrhea. In fact, the medication's prescribing information lists diarrhea as one of the common side effects of the weight loss medication.

In clinical trials, up to 23% of patients experienced diarrhea compared with only 8% of those taking a placebo. More specifically:

• 19% of people taking 5 mg of Zepbound reported diarrhea.

• 21% of people taking 10 mg of Zepbound reported diarrhea.

• 23% of people taking 15 mg of Zepbound reported diarrhea.

These statistics come from placebo-controlled weight-management trials of tirzepatide. Diarrhea was the second most common side effect (nausea came in first). According to the medication’s prescribing information, most instances of diarrhea occurred when patients increased their dosages and that the side effect subsided over time.

Just like with other GLP-1 (glucagon-like peptide-1) medications, the side effect seems to be dose-dependent, meaning it's more likely to occur at higher doses.

These numbers seem to be true outside of studies as well.

"In my practice, I see diarrhea in about a quarter of my patients taking Zepbound," says Allie Buttarazzi, MD, a board-certified internal medicine and lifestyle medicine physician. 

In addition to diarrhea, the common side effects of Zepbound include nausea, stomach pain, constipation, heartburn, indigestion, burping, injection site reactions, and fatigue.

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While diarrhea is the second most common side effect of Zepbound, experts don't completely understand why it happens with the medication. But it's most likely due to the ways Zepbound affects the digestive system.

Factors that can trigger diarrhea on Zepbound may include:

Gut motility changes

Research suggests GLP-1s have prominent direct effects on the GI tract, especially on motility (i.e. how food moves through the gut).

"Zepbound slows gastric emptying and alters gut hormone signaling, which can change how food moves through the intestines," says Supriya Rao, MD, a quadruple board-certified provider in internal medicine, gastroenterology, obesity, and lifestyle medicine. 

When food moves more slowly through your gut, it helps you feel full longer and eat less. But it also shifts your bowel habits. Some people experience constipation from the slower movement, while others may notice looser stools or diarrhea as their gut adjusts to treatment.

Gut bacteria changes

Early research suggests that semaglutide (the active ingredient in  Wegovy)  and tirzepatide (the active ingredient in Zepbound) may change the gut microbiome, but human evidence is limited. It is also not known whether these changes contribute to diarrhea, which may instead relate to how the medications affect digestion and gut movement. 

Increased bile acids in the gut 

Researchers don't fully understand the exact reasons behind GI side effects in people taking GLP-1s. But bile acids may be part of the story, according to Dr. Rao. 

Bile acids are digestive fluids that help your body break down fats. Zepbound may increase how much bile your liver makes, but research is still limited. In theory, extra bile could change the consistency of your stools, leading to diarrhea. 

How long Zepbound diarrhea lasts varies and depends on the individual and the dosage. 

Although it’s technically a dual GLP-1/GIP, Zepbound operates similarly and shares side effects with GLP-1 medications like Wegovy. And research suggests that diarrhea typically lasts for about three days in people taking GLP-1s for obesity. 

"Diarrhea is most common when someone first starts Zepbound or increases the dose," Dr. Buttarazzi says. "For most patients, it improves or even resolves with continued use [of the medication]."

Clinical trials note that diarrhea in participants was mild to moderate. However, if you have diarrhea that lasts more than 4–5 days, is not improving, or happens more than two times a day, Dr. Buttarazzi recommends contacting your healthcare provider.

"If it continues beyond a few weeks at a stable dose," Dr. Rao adds, "we might reassess and consider modifications." A dosage change or a new medication entirely may be warranted in some cases. And on that note…

Managing diarrhea on Zepbound typically involves staying hydrated, limiting caffeine intake, adjusting your eating habits, and more.

The good news? The side effect tends to be temporary, and there are a few ways you can attempt to alleviate your symptoms until it subsides. The strategies below are commonly used to manage diarrhea in general and may help ease symptoms while your body adjusts to the medication.

1. Stay hydrated

When you have a bout of diarrhea, you are essentially losing a lot of fluid from your body. If you have diarrhea too frequently, you could end up dehydrated, which would lead to thirst, fatigue, headache, dizziness, and less frequent urination. 

Dr. Buttarazzi recommends staying hydrated with oral rehydration solutions or electrolyte-rich fluids, such as coconut water, fruit juices, or broths.

You can also increase your fluid intake by drinking more water.

2. Limit caffeine and alcohol

Coffee can stimulate activity in the colon and trigger the urge to have a bowel movement in some people. If you notice that coffee makes your loose stools worse, consider temporarily cutting back while your diarrhea improves. Meanwhile, alcohol consumption can also cause or worsen diarrhea. 

Temporarily limiting coffee and alcohol may help keep your symptoms from getting worse.

3. Modify your meals

Try to eat meals regularly throughout the day and avoid foods that could aggravate diarrhea, such as fried foods. You may also want to limit dairy, spicy foods, or other items if you notice that they worsen your symptoms.

"Once rehydrated, I suggest small, frequent meals and avoiding dairy for a few days since lactose can be harder to digest during diarrheal episodes," Dr. Buttarazzi explains. "For my Zepbound patients, I also recommend avoiding large or high-fat meals, which can worsen nausea, vomiting, and diarrhea." 

Temporarily following a bland diet or a BRAT diet (bananas, rice, applesauce, toast) may also help treat Zepbound diarrhea. That’s because eating bland foods, such as bananas, toast, oatmeal, and applesauce, can help make stools firmer. 

"The BRAT diet is a simple and safe option when diarrhea flares," Dr. Rao explains. "It’s not meant as a long-term nutrition plan, but it can help settle the stomach and reduce stool frequency.”

4. Consider an over-the-counter medication

If you are experiencing diarrhea, you may consider trying over-the-counter (OTC) medications such as: 

• Pepto-Bismol (bismuth subsalicylate), which reduces inflammation in the intestine and decreases the flow of fluids and electrolytes into the bowel. 

• Imodium (loperamide), which slows intestinal movement and may reduce stool frequency by allowing more time for water and electrolytes to be absorbed.

An over-the-counter medication may be appropriate for some people with short-term diarrhea, but check the label and ask a healthcare professional if you have other medical conditions or take other medications.

"Supplements like probiotics, zinc, or psyllium husk fiber may help some people, but evidence is limited for medication-related diarrhea," Dr. Buttarazzi says. (Psyllium husk fiber is a supplement that's helpful for the GI in many cases: It helps with both diarrhea and constipation symptoms.)

However, before starting any new medication or supplement, you should discuss with your healthcare provider to ensure you don't have any medications or conditions that will interact. Once approved, always follow instructions on the medication label.

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Nausea may be the most common side effect of Zepbound, but diarrhea is a close second. Here’s what you need to know: 

• In clinical trials, up to 23% of people taking Zepbound experienced diarrhea.

• Researchers do not know exactly why Zepbound causes diarrhea, although the medication’s effects on the digestive system, specifically slowing down gut motility may contribute.

• Like other side effects, diarrhea is typically temporary and most common at the beginning of treatment and during dose escalation. 

• Staying hydrated, avoiding trigger foods, eating smaller meals, following a bland diet, and limiting caffeine and alcohol can help you manage Zepbound diarrhea.  

Just because it’s a common side effect of Zepbound doesn’t mean you shouldn’t contact your healthcare provider if you’re experiencing diarrhea. This is especially true if your symptoms are severe, are not improving or begin to significantly impact your quality of life. Your healthcare provider can determine if Zepbound is truly the cause and, if so, the best strategies for stopping your symptoms.