How Tirzepatide Affects Your Digestive System

Tirzepatide, known by the brand names Mounjaro and Zepbound, is an injectable drug approved by the US Food and Drug Administration (FDA) for the treatment of type 2 diabetes (T2D) and obesity. This medication mimics the action of two digestive hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), by binding to their receptors, which helps regulate blood sugar, appetite and digestion.

Despite its purported benefits, tirzepatide has been shown to cause gastrointestinal side effects. Continue reading to learn more about how tirzepatide moves through the digestive system and the potential side effects that may accompany that process.

Tirzepatide’s Impact on the Digestive System

Tirzepatide has notable effects on the actions of the digestive system, stemming from its interaction with the body’s gut hormones and gastrointestinal tract.

Dual Action on Gut Hormones

GIP and GLP-1 are natural hormones that help regulate blood sugar levels, notes Amy Nguyen, PharmD, a weight management pharmacist at Cedars-Sinai. GIP primarily stimulates the pancreas to release insulin and influences fat metabolism. GLP-1 boosts insulin, too, but it also suppresses glucagon (a hormone that helps maintain blood sugar levels), slows digestion, and helps reduce appetite. Together, GIP and GLP-1 play key roles in managing blood sugar.

In individuals with diabetes or obesity, these receptors often do not work effectively. Tirzepatide is designed to bind to both receptor types and give them a boost. This action allows people to feel fuller sooner, eat less, and experience lower blood sugar levels.

This drug is called a dual agonist because it binds to both GIP and GLP-1 receptors, meaning it activates two different receptors in the body simultaneously.

Medications like tirzepatide are formulated with a half-life of five days, helping people feel fuller for nearly a week after the injection of their dose, explains Ethan Lazarus, M.D., an obesity medicine physician in Colorado and past president of the Obesity Medicine Association.

Common Digestive Side Effects of Tirzepatide

Because of tirzepatide’s relationship with the digestive system, Dr. Nguyen says to watch for the following gastrointestinal side effects:

• Nausea and vomiting may result from slower digestion (delayed gastric emptying) and increased fullness, especially when first beginning the medication.
• Constipation may occur due to food’s slower transit time through the digestive system.
• Diarrhea may be experienced due to changes in gut hormones.
• Heartburn can also be caused by delayed gastric emptying.

Rare But Serious Digestive Side Effects of Tirzepatide

Though uncommon, tirzepatide can cause more serious gastrointestinal side effects.

Pancreatitis

A 2023 systematic review across five databases analyzed rates of adverse events associated with tirzepatide. According to the report, less than 1% of individuals taking three doses of tirzepatide experienced acute pancreatitis, which is inflammation of the pancreas. Though it is a rare condition, tirzepatide-related pancreatitis can manifest as severe abdominal pain, fever, nausea, and vomiting. Individuals experiencing those symptoms should stop tirzepatide and seek medical assistance in the emergency department, says Dr. Lazarus.

Gallbladder Disease

Gallbladder inflammation can also occur when taking tirzepatide. However, evidence of this finding is scarce, and more research is required to draw a definitive conclusion.

A 2022 trial published in the New England Journal of Medicine found a more frequent occurrence of gallbladder inflammation in people who took tirzepatide versus those who took a placebo. However, the overall incidence was very low, at 0.6% or below.

“Slower digestion can increase the risk of gallstones,” says Dr. Nguyen. “Symptoms of gallbladder problems may include pain in your upper stomach (abdomen), fever, yellowing of the skin or eyes (jaundice), and clay-colored stools.”

Indeed, some research indicates individuals with type 2 diabetes taking tirzepatide are at greater risk of developing gallbladder or biliary disease. However, more studies are needed to fully determine the association.

Intestinal Obstruction

Since tirzepatide delays gastric emptying and slows digestive movement, individuals taking the drug have an increased risk of intestinal blockages. This side effect also appears to be quite rare.

A 2023 case report outlines one person’s experience with a bowel obstruction of the large intestine while taking tirzepatide shortly after a dose increase. Another 2023 case study spotlights a similar situation, except the patient experienced a small bowel obstruction (SBO) after a recent switch to tirzepatide.

Both case studies only focused on one individual, and further research was recommended in each. Additionally, an earlier study found that patients taking drugs in the same class as tirzepatide had a higher risk of intestinal obstructions compared to those on other glucose-controlling medications.

Individuals taking tirzepatide who experience severe bloating or stomach pain should seek medical attention immediately.

Gastroparesis

Medications that slow gastrointestinal motility can cause symptoms similar to those of gastroparesis. The condition occurs when the stomach empties too slowly into the small intestine, leaving food and liquids in the stomach for longer than normal and resulting in bloating, nausea and stomach pain.

Some anecdotal evidence indicates a possible relationship between drugs like tirzepatide and gastroparesis, but additional studies are necessary to determine if there is a clear association.

Managing Digestive Side Effects of Tirzepatide

Some measures that can be considered to help minimize common side effects of tirzepatide:

• Adjusting doses gradually: Individuals beginning tirzepatide should consider starting at a low dose and increasing it gradually, says Dr. Nguyen. This practice can help the body adjust to the medication and minimize gastrointestinal side effects, she adds.
• Reducing meal size: Eating frequent small meals for the first few days after your first dose might help mitigate side effects, says Dr. Lazarus. He also recommends staying hydrated and eating small portions of plants and proteins. Reducing meal size and focusing on nutrient-dense foods facilitate easier digestion, potentially helping with nausea or stomach discomfort.
• Chewing food well: Chewing food thoroughly helps break it down into smaller pieces that can move through the digestive tract more easily.
• Avoiding high-fat/high-sugar/artificially sweetened/highly processed foods: These foods can worsen symptoms, says Dr. Lazarus.
• Consulting with a healthcare professional: Regular check-ins with a prescriber are critical for individuals beginning any new medication. Always contact your doctor or seek medical attention if you’re experiencing negative side effects after receiving tirzepatide.

Tirzepatide’s Long-Term Effects on Digestion

Tirzepatide can be a lifelong medication for some people, explains Dr. Nguyen, so understanding the long-term impacts of this drug is important. Research to this point has only evaluated the effects of tirzepatide over the course of approximately three years. Given the difference between the relatively short duration of clinical trials for this drug and the longer periods of use recommended by many doctors, individuals taking tirzepatide should work with their prescribers to weigh the risks and benefits involved in the continued use of this medication.