Why does Zepbound cause diarrhea?

In this article:

• Zepbound diarrhea
• Why does it cause diarrhea?
• Other side effects
• Managing diarrhea
• When to see a doctor
• The bottom line

In this article

• Zepbound diarrhea
• Why does it cause diarrhea?
• Other side effects
• Managing diarrhea
• When to see a doctor
• The bottom line

Tirzepatide is the active ingredient currently found in two brand-name medications, Zepbound and Mounjaro. It belongs to a class of medications called dual GIP/GLP-1 receptor agonists, which work by activating two hormone pathways: the GIP pathway and the GLP-1 pathway.

Zepbound is FDA approved for adults with obesity, for adults who are overweight with at least one weight-related health problem, and for adults with obesity who also have moderate-to-severe obstructive sleep apnea (OSA). 

While very effective for weight loss, Zepbound can cause gastrointestinal (GI) side effects, including diarrhea, in some people. Here’s why, what can be done about it, and when it becomes serious.

Does Zepbound cause diarrhea?

“Diarrhea is a known side effect of Zepbound,” says Supriya Rao, MD, a quadruple board-certified healthcare provider based in the Greater Boston area. 

The medication label warns that diarrhea is a common adverse reaction. In fact, the most common side effects of tirzepatide are those that affect the GI tract, including nausea, vomiting, and diarrhea. Clinical trials show that up to 49% of people taking the medication will experience adverse GI effects. The likelihood increases with higher doses. Diarrhea specifically occurs in an estimated 16.24% of tirzepatide users.

“It’s fairly common, but it doesn’t happen to everyone taking the medication,” Dr. Rao says. When diarrhea does occur from Zepbound use, it tends to be mild to moderate in severity.

Why does Zepbound cause diarrhea?

The link between Zepbound and GI side effects, like diarrhea, can be explained by how the medication works.

GLP-1 agonists function by stimulating insulin secretion, reducing blood sugar levels, and managing metabolism, which helps explain why they’re used to treat Type 2 diabetes and obesity. Additionally, Zepbound is also a GIP agonist, which has similar effects on insulin secretion and satiety. Dual GIP/GLP-1 agonists, such as Zepbound, may be more effective at reducing body weight than GLP-1 agonists alone, research suggests. However, they may also come with a higher prevalence of diarrhea.

What’s more, GLP-1 and GIP are gut hormones. Unsurprisingly, activating receptors for them could have consequences for the gut. “Zepbound works by slowing stomach emptying and changing the way the gut processes food,” Dr. Rao explains. “For some, as their digestive system adapts, this can lead to looser stools, more frequent bowel movements, or diarrhea.”

How long does Zepbound diarrhea last?

Diarrhea is one of the potential side effects of Zepbound, and a common one at that, but there’s some good news: It’s usually temporary and often resolves over time. Here’s when it typically occurs and how long it can last.

“You’re most likely to experience diarrhea during the initial phase,” says Michael Glickman, MD, an obesity medicine specialist in Washington, DC. This refers to the starter dose of Zepbound. A once-weekly injection, Zepbound is administered using single-dose pens or vials. The manufacturer’s recommendation is to begin at the lowest dose, 2.5 mg, and increase the dosage every four weeks until the maintenance dose is achieved. The maximum dose is 15 mg, but not everyone titrates all the way up. Your provider will help you determine the lowest dose that’s effective for you.

Fortunately, Zepbound-induced diarrhea typically lasts only a few days. Research on GLP-1 medications suggests that diarrhea is most likely to occur during the first four weeks of treatment, typically lasting for about three days and decreasing notably over time. “There’s a noticeable trend of improvement over time on a maintenance dose,” Dr. Glickman says. “With enough time, the gut adapts to these motility changes.”

However, there’s another trend to be aware of, which is that side effects can also occur after a dose increase, Dr. Rao points out. Some research suggests that most GI side effects from tirzepatide occur during dose escalation, though they were non-serious.

Should Zepbound cause diarrhea, it likely won’t last forever. “I’ve seen diarrhea decrease significantly within two to four weeks and resolve completely with time,” Dr. Rao says. “Of course, some patients may continue to have intermittent symptoms, but they are often mild and manageable.”

Other possible Zepbound side effects

Though common, diarrhea isn’t the only side effect of Zepbound. Other common side effects of Zepbound include:

• Nausea
• Vomiting
• Constipation
• Abdominal pain
• Dyspepsia
• Injection site reactions
• Fatigue
• Hypersensitivity reactions
• Burping
• Hair loss
• Gastroesophageal reflux disease (GERD)

“In contrast to diarrhea, some patients experience constipation with similar trends in severity,” Dr. Glickman says.

It’s also possible for serious side effects to occur. Tirzepatide can also cause:

• Allergic reactions
• Vision changes
• Dehydration
• Irregular heart rate
• Gallbladder problems, such as gallstones
• Kidney injury
• Pancreas problems, such as pancreatitis
• Thyroid cancer, such as medullary thyroid carcinoma

Notify a healthcare provider if you experience stomach pain that won’t go away, signs of a severe allergic reaction, or other unusual problems.

Managing diarrhea while taking Zepbound

Diarrhea while taking Zepbound is often mild and temporary, but that doesn’t mean it’s pleasant. Fortunately, there are several steps you can take to manage this.

1. Consult your prescribing healthcare provider

“Patients who have the best outcomes taking Zepbound tend to strictly follow the direction of their prescribing doctor,” Dr. Glickman says. 

This can include sticking to the dose escalation schedule of your medication. “Most often, prescribers will start at the lowest dose and titrate conservatively based on the patient’s needs and tolerance,” Dr. Glickman explains. “This significantly diminishes the side effect profile.” 

This can also include seeking medical help when necessary or asking your provider for tailored medical advice. If your symptoms aren’t letting up, it’s a good idea to let them know what’s going on. They may be able to suggest lifestyle changes and medications.

2. Implement practical lifestyle changes

Tirzepatide can affect the gut, so it makes sense to adjust your diet accordingly. “Avoid heavy, high-fat meals that place stress on the gut,” Dr. Rao says. She also recommends adjusting your dietary fiber intake. “You may need to add soluble fiber or you may need to reduce it until symptoms settle,” Dr. Rao says.

Other lifestyle changes to alleviate diarrhea can include:

• Eating smaller, more frequent meals
• Get plenty of fluids
• Replenish electrolytes with broths and sports drinks

3. Try over-the-counter remedies

Ask your healthcare provider if anti-diarrhea medications, such as Imodium A-D (loperamide) are suitable for you.

In severe cases, your provider may recommend electrolytes to replenish lost fluids and avoid dehydration, but not as a cure for diarrhea.

When to see a provider about Zepbound diarrhea

Diarrhea is a known and common side effect of Zepbound. In many cases, Zepbound-induced diarrhea typically does not require medical attention unless it’s persistent and severe.

“Most often for mild symptoms, medical attention is not necessary,” Dr. Glickman says. However, he recommends seeing a healthcare professional for the following:

• Signs of dehydration (e.g.,  dark and decreased urine, dizziness, dry mouth, rapid pulse, etc.)
• Severe abdominal pain
• Persistent vomiting

Bottom line: Zepbound diarrhea is typically mild

Will you experience diarrhea while taking Zepbound? It’s possible. However, most people taking tirzepatide don’t have diarrhea, though they may experience other GI side effects (namely, nausea).

Still, any diarrhea that results from Zepbound usage is usually temporary and manageable. It often resolves over time, but if it doesn’t or you notice other unusual problems, contact a healthcare professional with your concerns.