Does Zepbound cause diarrhea?

It's normal to experience side effects when starting a new medication. But due to the media attention around newer weight loss medications, you may be even more concerned about the side effects of Zepbound (tirzapetide). Specifically, many worry about "Zepbound diarrhea," what people who take the medication casually refer to as one of the side effects. 

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 drug'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 to 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 a phase 3 trial of tirzapetide. Diarrhea was the second most common side effect in the study (nausea came in first). The study noted that 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 is more likely to occur (and be worse) 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 drug. But it’s most likely due to the ways Zepbound affects the digestive system. 

Quick refresher: Zepbound works by mimicking hormones — GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) — that help control blood sugar and appetite. It delays gastric emptying, slowing how quickly food moves through your digestive tract. 

This can help you feel fuller longer, eat less, and lose weight. But it can also lead to gastrointestinal (GI) side effects, such as diarrhea and — to make matters more complicated — constipation. (Yup, the same drug that may have you running to the loo can also leave you stuck on the toilet.)

Let’s take a closer look at what may be happening in your body that can trigger diarrhea on Zepbound.

Gut motility changes

Studies show 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," explains Supriya Rao, MD, DABOM, DABLM, 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

GLP-1s like Wegovy (semaglutide) and dual GLP-1/GIPs like Zepbound have been shown to change the gut microbiome. In other words, they can throw off the balance of microorganisms that support digestion, nutrition, immunity, and several other functions. And this can lead to GI side effects, such as, yup, diarrhea. 

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. That 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 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 and even stopping diarrhea on Zepbound typically involves staying hydrated, limiting caffeine intake, adjusting your diet, 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.

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, and dizziness. 

Dr. Buttarazzi recommends staying hydrated with oral rehydration solutions or electrolyte-rich fluids, such as coconut water, fruit juices, or broths. But be sure to pay attention to salt or sugar content, as added sugar and sodium can worsen side effects and inhibit your weight loss goals on Zepbound. 

You can also just keep up your fluid intake by sipping on water — no need to worry about calories or added ingredients that way, too. 

2. Limit caffeine and alcohol

Caffeine is negatively associated with chronic diarrhea. That’s because it can increase the activity of the colon. Meanwhile, alcohol consumption can also cause or worsen diarrhea. So, cutting back on your daily cups of Joe and glasses of wine may help alleviate Zepbound diarrhea. 

3. Modify your meals

The experts interviewed recommended eating smaller meals throughout the day and avoiding foods that could aggravate diarrhea, such as fried foods, dairy, and spices. And clinical studies also support this approach. 

"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." 

Following a bland diet or a BRAT diet 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 struggling to get a handle on your diarrhea symptoms, 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 bowel movements, allowing more water and electrolytes to be absorbed, and reduces frequency. 

"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.

• Zepbound may cause diarrhea because of its effects on the digestive system, specifically slowing down gut motility, disrupting the microbiome, and increasing bile acids in the gut. 

• 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 last more than 4–5 days 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.