Why does tirzepatide cause diarrhea? A guide to managing GLP-1 GI side effects

Key Points:

• Tirzepatide (Zepbound, Mounjaro) causes diarrhea primarily because its GLP-1 component alters how food moves through your entire digestive tract.
• Diarrhea is one of the most common gastrointestinal side effects of tirzepatide, but it is usually mild and temporary.
• The key to managing this side effect is focusing on hydration with electrolytes and temporarily shifting to a low-fiber, low-fat diet until symptoms stabilize.

If you’ve recently started taking tirzepatide – the active ingredient in Zepbound® for weight loss and Mounjaro® for type 2 diabetes – you may be experiencing diarrhea. While this a frustrating side effect, you can take comfort in knowing that you’re not alone.

Diarrhea is one of the most common side effects associated with this powerful medication, and it can be frustrating, uncomfortable, and of course, disruptive to your daily life. It’s natural to want to know why this is happening and, more importantly, how to make it stop.

The answer lies in how the drug works on your gut hormones, which can cause a big shift in your body’s internal plumbing. Here’s a look at the evidence-based mechanisms behind this side effect and the practical, dietitian-approved steps you can take to manage it.

How tirzepatide affects digestion

Tirzepatide is referred to as a "dual agonist" medication because it works by mimicking two natural hormones in your body: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).

These hormones act on your metabolism and appetite, but they also have a powerful, direct effect on your entire digestive system.

“Tirzepatide controls appetite, slows digestion, and reduces blood sugar levels. Sometimes the slowing of digestion leads to diarrhea,” explains Rita Restivo, RD.

The dual action mechanism: GLP-1 and GIP

Research suggests that GLP-1 receptor agonism is the primary driver of the slowed gastric emptying that contributes to many gastrointestinal side effects.

GLP-1 is responsible for two main functions that aid in blood sugar control and weight loss:

• It signals the brain that you are full, which reduces your appetite.
• It dramatically slows gastric emptying, meaning food stays in your stomach longer.

GIP works alongside GLP-1 to enhance insulin secretion and improve overall metabolic health. While GIP may contribute to the drug's effectiveness, its role in directly causing diarrhea is considered minor compared to the potent effects of GLP-1.

Why tirzepatide causes diarrhea

While slowed gastric emptying is often cited as the main reason for side effects like nausea and feeling full sooner than normal, the root of tirzepatide-related diarrhea is more complex. It involves changes further down your digestive tract.

Your body naturally absorbs water and nutrients as food moves from the stomach to the intestines and eventually to the colon. But tirzepatide disrupts this delicate balance.

While tirzepatide slows how quickly food leaves your stomach, it actually may increase intestinal transit time by altering the natural muscular contractions (motility) of your intestines. This reduces the time available for water absorption in the colon, leading to loose stools.

The rapid movement of contents through the lower intestinal tract means there’s less time for water to be properly absorbed into your body, which results in the loose, watery stools characteristic of diarrhea.

How common is diarrhea with tirzepatide?

While diarrhea can be a frustrating side effect, it may help to know that it’s quite common among tirzepatide patients.

Diarrhea is consistently reported as one of the most common gastrointestinal side effects for people taking tirzepatide, typically only outranked by nausea.

The actual prevalence varies slightly depending on the patient population and the dose:

• In people with type 2 diabetes (T2D): The rate of diarrhea was significantly higher on tirzepatide compared to other medications used for diabetes management.
• In weight management studies: Clinical trials showed the incidence of diarrhea ranging from 12% to 22% of participants, depending on the dosage.
• Dose-dependent effect: Gastrointestinal side effects, including diarrhea, are generally dose-dependent, meaning the higher the dose, the more likely you are to experience them.

When will the diarrhea stop?

The good news is that for most people, this side effect is temporary.

Diarrhea and other GI adverse events are typically temporary and only mild to moderate. You are most likely to experience these issues during the initial phase of treatment or immediately after a dose increase  – the period when your body is adjusting to a higher level of the medication.

As your body adapts to the new drug, the incidence and intensity of these events decrease over time. If you've been on a stable dose for several weeks and your symptoms haven't improved, you should talk to your healthcare provider.

Nutrition strategies for diarrhea relief

Since tirzepatide works by affecting how your body processes food, your strategy for managing diarrhea should focus on what you eat and how you eat it.

A qualified registered dietitian is the best partner for creating a tailored plan that eases these symptoms while ensuring you maintain proper nutrition. A registered dietitian can help you create a personalized plan that minimizes discomfort.

“I suggest that clients eat smaller and more frequent meals, avoid high fat and greasy foods, increase fiber gradually, and stay hydrated,” says Rita Restivo, RD. “If the diarrhea persists, contact a healthcare provider for potential dose adjustments or follow up.”

Prioritize rehydration & electrolytes

Diarrhea can quickly lead to dehydration. This is the most crucial step to manage.

When you have diarrhea, you lose essential minerals (electrolytes) like sodium and potassium. You should focus on replacing these, not just drinking water.

• Sip on low-sugar electrolyte solutions or diluted sports drinks
• Savory options like chicken or vegetable broth and bone broth can replace lost sodium
• Even diluted fruit juice (like apple or pear) can help replenish potassium
• Sip on fluids frequently throughout the day instead of drinking large amounts at once, which can sometimes worsen symptoms

Be strategic with fiber

When you are constipated on tirzepatide, increasing fiber is the right move. However, when you have active diarrhea, you need to be more strategic with what kind of fiber you consume.

Clinical recommendations for managing GLP-1 side effects suggest adding more soluble fiber for those with constipation but avoiding high-fiber foods for diarrhea until symptoms improve.

You should temporarily avoid:

• Insoluble fiber: The tough, structural fiber found in vegetable skins, stalks, whole-wheat bread, and most raw vegetables. This type of fiber can speed up intestinal movement, which will make diarrhea worse.
• Cruciferous vegetables: Broccoli, cauliflower, and cabbage can produce excess gas, adding to the general discomfort of a volatile GI tract.
• Dairy: Many people find that lactose can exacerbate diarrhea.

Instead, you should temporarily focus on easily digestible, binding foods that contain soluble fiber (which dissolves in water to form a gel), such as:

• Bananas, avocado, peas, beans, and carrots
• Unsweetened applesauce or cooked apples
• White rice
• Dry toast
• Oats
• Psyllium husk

Soluble fiber adds bulk and slows things down in the digestive tract.

Choosing foods that soothe

The rule of thumb here is to keep things bland, soft, and easy on the fat. Since high-fat foods take longer to digest and can exacerbate an already-sensitive gut, keeping your fat intake low during an acute episode is vital.

Temporarily focus on these easy-to-digest options:

• Starches: White rice, rice cakes, saltine crackers, white toast, plain mashed potatoes (avoiding heavy butter/cream)
• Proteins: Lean sources like baked or grilled chicken breast (skinless), baked fish, or eggs
• Fruits: Bananas, unsweetened applesauce, and canned peaches
• Vegetables: Cooked carrots, soft squash, or peeled, seedless vegetables

You should also temporarily avoid two major categories of gut irritants:

• Spicy foods: Chili peppers and strong spices can irritate the stomach lining
• Simple sugars/sweeteners: Sugary drinks and products containing artificial sweeteners or sugar alcohols (like sorbitol or xylitol) can draw water into the colon, making diarrhea worse

Eating small, frequent, low-fat meals

Eating a large meal sends a strong signal to your digestive system, which can trigger the motility changes that cause diarrhea. To combat this, you should try to:

• Eat smaller portions: Reduce your meal size by about a third or half
• Eat more often: Instead of three large meals, aim for five or six mini-meals throughout the day
• Chew thoroughly: Take your time and chew your food until it is soft to give your stomach a head start on digestion

When to consult your care team

While mild-to-moderate diarrhea is common and typically resolves on its own, severe or persistent symptoms require immediate professional attention.

You should contact your healthcare provider if you experience any of the following:

• Signs of dehydration: Feeling excessively thirsty, having a very dry mouth, urinating less often, or having dark-colored urine. This is a critical sign, as severe gastrointestinal symptoms leading to dehydration can be linked to acute kidney injury in some cases.
• Severe or persistent diarrhea: Diarrhea that lasts longer than two to four weeks, or if it suddenly becomes more frequent and watery.
• Worsening symptoms: Diarrhea combined with severe nausea, vomiting, or abdominal pain that is intolerable.

Your prescribing physician can evaluate your symptoms and determine if an adjustment to your dosage is needed. They may also temporarily pause your tirzepatide treatment until your symptoms stabilize.

In partnership with your doctor, a registered dietitian who specializes in weight management and GLP-1 medications is an invaluable resource. They can pinpoint nutritional deficiencies caused by food avoidance, help you manage a low-fiber phase, and guide you back to a more balanced diet as your body adjusts to the medication. They may also have experience addressing gut health issues such as constipation that can also occur on this class of medication.

Final thoughts

Experiencing diarrhea on tirzepatide can be frustrating, but remember that it is a common side effect of the drug working exactly as intended to slow your digestion. For the vast majority of people, these symptoms are a temporary hurdle, not a permanent roadblock.

By proactively focusing on replacing lost electrolytes, choosing easily digestible foods, and following an intentional, low-fat, low-fiber diet during acute episodes, you can minimize the discomfort.

Get the support you need to manage digestive issues and meet your goals on tirzepatide. Connect with a registered dietitian covered by your health insurance now.

Frequently asked questions (FAQs)

How long does tirzepatide diarrhea typically last?

For most people, diarrhea and other gastrointestinal side effects are temporary and last a few days to a few weeks. They are most common when you first start the medication or when your dose is increased. If the diarrhea persists beyond four to six weeks at a stable dose, consult your prescribing physician.

What foods should I avoid when experiencing diarrhea on tirzepatide?

When experiencing diarrhea, you should temporarily avoid high-fat foods (fried foods, heavy sauces), spicy foods, and high-fiber foods (raw vegetables, whole grains, nuts, seeds) that can increase intestinal motility.

Should I skip a dose if my diarrhea is severe?

No. You should never skip or change your dose without first consulting your healthcare provider.

If your diarrhea is severe, persistent, or accompanied by signs of dehydration (excessive thirst, dry mouth), you should contact your doctor immediately. They will determine the safest course of action, which may involve temporarily reducing the dose or stopping treatment until the symptoms resolve.

The views expressed by authors and contributors of such content are not endorsed or approved by Fay and are intended for informational purposes only. The content is reviewed by Fay only to confirm educational value and audience interest. You are encouraged to discuss any questions that you may have about your health with a healthcare provider.