Does tirzepatide cause diarrhea?

GLP-1 medications, such as semaglutide (Wegovy, Rybelsus, and Ozempic), are notorious for causing gastrointestinal (GI) side effects, including nausea, vomiting, abdominal pain, and diarrhea. Tirzepatide (Mounjaro and Zepbound) — dual GLP-1/GIP agonists — can come with these side effects, too. Whether it is used for diabetes or weight loss, tirzepatide commonly causes diarrhea. So, why does tirzepatide cause diarrhea, and how can you manage tirzepatide diarrhea? 

Keep reading to understand the relationship between tirzepatide and diarrhea, and how to manage this unpleasant side effect.

Yes, diarrhea is one of the most common side effects of Mounjaro and Zepbound, both of which are brand-name drugs that contain tirzepatide as their active ingredient. In clinical trials of Mounjaro, 12%--17% of adults who took the drug for type 2 diabetes experienced diarrhea, compared to only 9% of those who took a placebo. 

Similarly, in studies of Zepbound, 19%--23% of adults who took tirzepatide for weight loss reported having diarrhea; this was the case for just 8% of those who took a placebo. 

In studies of both Mounjaro and Zepbound, the majority of cases occurred when the medication dosage was increased, and GI side effects were usually mild to moderate and decreased over time.

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Although diarrhea is common with tirzepatide, experts don’t fully understand why the drug can often cause you to feel glued to the toilet. Complicating things further, some people may even experience the opposite — constipation — on tirzepatide. The way the drug works on the digestive system is the most likely reason.

Here’s how it works. Tirzepatide exerts its effects on weight loss and blood sugar by mimicking two naturally occurring hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Through this mechanism, tirzepatide helps regulate your blood sugar and lower your appetite by encouraging more insulin release, decreasing glucose production, and slowing gastric emptying (i.e., the movement of food through the digestive tract). Its mechanism of action can lead to diarrhea in several ways. 

Delaying gastric emptying

GLP-1 medications, along with dual agonists like tirzepatide, affect gut motility (the movement of food through the digestive tract) and slow gastric emptying (keeping food in the stomach for longer). While these effects can help with appetite reduction and blood sugar regulation, they can also alter normal digestion patterns and bowel movements. 

Changing the intestinal environment

Your gut is filled with trillions of microorganisms that comprise the gut microbiome. These organisms play an integral role in your health by supporting digestion, nutrition, immunity, and several other functions. Everyone’s gut microbiome is unique, and sometimes, dietary changes or medications can alter your intestinal environment.

GLP-1 and dual GLP-1/GIP therapies appear to change the gut microbiome. These changes may lead to GI side effects, such as nausea, abdominal distension, constipation, and diarrhea. However, the relationship seems to be complex, and researchers are still working to understand exactly how these medications and gut bacteria interact.

Increasing fluid secretion

Tirzepatide increases the levels of gut hormones, such as GIP. This can lead to increased intestinal fluid secretion, which can contribute to loose and watery stools.

It varies from person to person. Tirzepatide has a similar side effect profile as GLP-1 medications, and research has shown that diarrhea typically lasts for about three days in people who take GLP-1s for obesity. 

According to studies of Mounjaro and Zepbound, diarrhea is most likely to occur when first starting treatment or raising your dosage, especially during the first four weeks of treatment. It is also more likely if you’re taking a higher dose of tirzepatide. In most cases, diarrhea is temporary and will improve as you get used to the medication. Nevertheless, if your diarrhea is severe or isn’t improving, consult your healthcare provider. 

While most reports of diarrhea are mild and temporary, it can still be an uncomfortable side effect that affects your daily life. Fortunately, there are several ways to manage tirzepatide diarrhea, such as staying hydrated and modifying your diet. 

Stay hydrated

Diarrhea can increase your risk of dehydration, so it is important to stay hydrated. Drink clear liquids, such as water, diluted fruit juices, or sports drinks (just be careful about drinking high-sugar or high-calorie drinks, especially if you’re trying to manage your diabetes or weight). 

Avoid trigger foods

Keeping track of what you eat and your bowel movements can help determine which foods are triggering diarrhea. Certain foods are known to soften the stool and should be limited or avoided if you’re having diarrhea. These include: 

• Dairy and dairy products

• Fried or greasy food

• Fiber-rich foods

Limit caffeine and alcohol

Caffeine can increase the activity of the colon and worsen diarrhea. Similarly, binge drinking has been linked to diarrhea. Therefore, if you’re experiencing tirzepatide diarrhea, it’s a good idea to steer clear of caffeine and alcohol. 

Adjust your diet

A bland diet, or BRAT diet, can make stools firmer by easing the workload of your digestive system. Examples of bland foods include bananas, toast, oatmeal, white rice, applesauce, and broth. 

Consider over-the-counter (OTC) medications

OTC antidiarrheal medications, such as loperamide (Imodium) and bismuth subsalicylate (Pepto-Bismol), may provide short-term relief. Loperamide slows down the movement of food and waste in the digestive tract, which allows the body more time to absorb water from stools. This helps firm up stools. Bismuth subsalicylate produces its antidiarrheal effects by reducing inflammation, limiting intestinal secretions, and promoting fluid and electrolyte reabsorption. It also has some mild antimicrobial effects, but it does not significantly alter normal gut bacteria.

However, like all medications, these options come with risks and may not be safe for everyone. Be sure to review the product warnings and follow the directions on the label. Reach out to your healthcare provider for guidance if diarrhea lasts more than two days despite taking OTC antidiarrheal medications. 

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Bottom line

If you’re taking Mounjaro or Zepbound and find yourself having diarrhea, your medication may be the culprit. Here are some key points to keep in mind if you’re having tirzepatide diarrhea:

• Mounjaro and Zepbound commonly cause diarrhea. In studies, up to 17% of people taking Mounjaro reported diarrhea, while up to 23% of people taking Zepbound reported this side effect. In most cases, this effect is temporary, and improves as your body adjusts to the medication.

• Diarrhea occurs due to tirzepatide’s effects on the digestive system. The medication can delay gastric emptying, alter the gut microbiome, and increase intestinal fluid secretion, all of which can lead to diarrhea. 

• Luckily, there are several ways to manage tirzepatide diarrhea, including staying hydrated, avoiding trigger foods, limiting caffeine and alcohol, eating a bland diet, and taking OTC medications if appropriate. 

If you’re having tirzepatide diarrhea, it may be a good idea to speak to your healthcare provider. They can help determine if tirzepatide is the cause, and if so, they can recommend the best strategies to manage your symptoms. Aside from the strategies mentioned above, they may also adjust your medication dosage or switch you to an alternative treatment.