Do You Get Constipated on Zepbound? Causes and Management

Constipation is a recognized gastrointestinal side effect of Zepbound (tirzepatide), occurring in approximately 17-24% of patients in clinical trials. While less common than nausea or diarrhea, constipation can affect individuals using this dual GIP/GLP-1 receptor agonist for chronic weight management. Zepbound slows gastric emptying and intestinal motility as part of its mechanism to reduce appetite and support weight loss, which can lead to harder, drier stools. Most cases are mild to moderate and improve with time, though some patients require management strategies. Understanding this potential side effect and implementing preventive measures can help optimize treatment outcomes while maintaining bowel regularity.

We offer compounded medications and Zepbound®. Compounded medications are prepared by licensed pharmacies and are not FDA-approved. References to Wegovy®, Ozempic®, Rybelsus®, Mounjaro®, or Saxenda®, or other GLP-1 brands, are informational only. Compounded and FDA-approved medications are not interchangeable.

Does Zepbound Cause Constipation?

Yes, constipation is a recognized gastrointestinal side effect of Zepbound (tirzepatide), though it occurs less frequently than other digestive symptoms such as nausea or diarrhea. According to the FDA prescribing information, constipation is listed among the common adverse reactions in clinical trials, with incidence varying by dose. Zepbound is approved for chronic weight management in adults with obesity or overweight with at least one weight-related comorbidity, and is intended for use with a reduced-calorie diet and increased physical activity. It works by activating both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors.

The dual agonist mechanism of tirzepatide affects gastrointestinal motility, which can lead to slower movement of food through the digestive tract. This slowing effect, while beneficial for appetite regulation and glycemic control, may result in constipation for some patients. It is important to note that individual responses vary considerably—some patients experience no constipation at all, while others may find it bothersome enough to require management strategies.

Constipation associated with Zepbound is generally mild to moderate in severity and often improves as the body adjusts to the medication, though persistence can occur in some patients. Understanding this potential side effect before starting treatment allows patients and healthcare providers to implement preventive measures early. Patients should be aware that gastrointestinal symptoms, including constipation, are among the most commonly reported adverse effects with GLP-1 receptor agonists and dual agonists like Zepbound, and these effects are typically dose-related and frequently improve over time. Notably, Zepbound is not recommended for patients with severe gastrointestinal disease, including severe gastroparesis.

Why Gastrointestinal Side Effects Occur with Zepbound

Zepbound's mechanism of action directly explains why gastrointestinal side effects, including constipation, occur. Tirzepatide activates GIP and GLP-1 receptors located throughout the gastrointestinal tract, pancreas, and central nervous system. These receptors play crucial roles in regulating appetite, glucose metabolism, and gastric emptying. When activated, they slow the rate at which the stomach empties its contents into the small intestine—a process called delayed gastric emptying.

Delayed gastric emptying contributes to increased satiety and reduced appetite, which are therapeutic benefits for weight management. However, this same mechanism can lead to constipation when intestinal transit time becomes excessively prolonged. The medication essentially slows down the entire digestive process, allowing more water to be absorbed from the stool as it moves through the colon, resulting in harder, drier stools that are more difficult to pass.

Additionally, GLP-1 receptor activation affects the enteric nervous system, which controls gut motility and secretion. This can reduce the frequency and strength of intestinal contractions (peristalsis) needed to move stool through the colon efficiently. Delayed gastric emptying is typically most pronounced early in treatment and following dose escalations.

Other contributing factors include dietary changes that often accompany weight loss treatment. Patients may inadvertently reduce fiber intake when decreasing overall food consumption, or they may not adjust fluid intake appropriately. Reduced physical activity due to caloric restriction can also contribute to constipation, creating a multifactorial situation that requires comprehensive management.

How Common Is Constipation on Zepbound?

In the SURMOUNT clinical trial program that led to Zepbound's FDA approval for weight management, constipation was reported as a common adverse reaction. According to the FDA prescribing information for Zepbound, constipation occurred in approximately 17-24% of patients receiving tirzepatide across the 5 mg, 10 mg, and 15 mg doses, compared to about 11% in the placebo group in the SURMOUNT-1 trial. This indicates a dose-related increase attributable to the medication.

While constipation is common, other gastrointestinal side effects such as nausea, diarrhea, and vomiting were also frequently reported. Gastrointestinal adverse reactions were most common during the dose escalation period and typically decreased over time with continued treatment. The majority of patients who experienced constipation reported it as mild to moderate in severity, with few discontinuations due to this specific side effect.

It is important to recognize that clinical trial populations may not fully represent real-world experience. Individual susceptibility to constipation varies based on baseline bowel habits, dietary patterns, hydration status, concurrent medications, and underlying conditions. Patients with a history of chronic constipation or irritable bowel syndrome with constipation may be at higher risk when starting Zepbound.

The dose-escalation schedule used with Zepbound—starting at 2.5 mg weekly and gradually increasing every four weeks—is designed partly to minimize gastrointestinal side effects. This gradual titration allows the digestive system time to adapt to the medication's effects on motility. Most gastrointestinal symptoms, including constipation, tend to be most prominent during the initial weeks of treatment or following dose increases, then often improve with continued use.

Managing and Preventing Constipation While Taking Zepbound

Effective management of constipation while taking Zepbound involves both preventive strategies and treatment interventions. Dietary modifications form the foundation of prevention. Patients should aim for 25-35 grams of fiber daily through whole grains, fruits, vegetables, legumes, and nuts. Gradually increasing fiber intake helps avoid bloating and gas. Soluble fiber sources like oats, psyllium, and flaxseed are particularly beneficial as they add bulk and soften stool.

Adequate hydration is critical—patients should generally consume at least 64 ounces (eight 8-ounce glasses) of water daily, and potentially more with higher fiber intake or in hot weather. However, patients with heart failure, chronic kidney disease, or other conditions requiring fluid restriction should follow their healthcare provider's specific guidance. Proper hydration prevents excessive water absorption from the colon, keeping stools softer and easier to pass. Warm liquids, particularly in the morning, can stimulate bowel movements.

Regular physical activity promotes intestinal motility through mechanical stimulation and improved circulation to the digestive tract. Even moderate activity such as 30 minutes of walking daily can significantly improve bowel regularity. Patients should not allow reduced appetite to lead to complete sedentary behavior.

Over-the-counter interventions can be helpful when lifestyle measures are insufficient. Bulk-forming laxatives (psyllium, methylcellulose) are generally first-line and safe for regular use. Osmotic laxatives such as polyethylene glycol (MiraLAX) are considered first-line treatments that can be used safely for longer periods if needed. Magnesium hydroxide (Milk of Magnesia) draws water into the intestines but should be used with caution in patients with kidney disease due to potential magnesium accumulation. Stool softeners (docusate) may provide relief for some patients, though evidence for their effectiveness is limited.

Stimulant laxatives (bisacodyl, senna) are best used intermittently or for short courses rather than daily management, as they may cause cramping and electrolyte disturbances with prolonged use. Patients should establish a regular bathroom routine, allowing adequate time after meals when the gastrocolic reflex naturally stimulates bowel movements.

If gastrointestinal side effects become bothersome, patients may need to pause dose escalation or temporarily return to a lower dose of Zepbound, in consultation with their healthcare provider. For persistent constipation despite these measures, prescription medications may be considered.

When to Contact Your Healthcare Provider

While mild constipation can often be managed with lifestyle modifications and over-the-counter remedies, certain situations warrant prompt medical evaluation. Patients should contact their healthcare provider if constipation persists for more than one week despite self-care measures, as this may indicate the need for prescription interventions or dose adjustment of Zepbound.

Severe abdominal pain or distension accompanying constipation requires immediate medical attention, as these symptoms could indicate bowel obstruction or other serious complications. Similarly, rectal bleeding, black or tarry stools, or blood in the stool should prompt urgent evaluation to rule out gastrointestinal injury or other pathology unrelated to Zepbound.

Nausea and vomiting that prevent adequate oral intake, particularly when combined with constipation, may indicate more significant gastrointestinal dysfunction. Cases of gastroparesis and ileus have been reported with GLP-1-based therapies, though causality is uncertain. Zepbound is not recommended in patients with severe gastroparesis. If severe or persistent gastrointestinal symptoms occur, withhold further doses and contact your healthcare provider.

Other concerning features include fever, inability to pass gas, persistent vomiting, unexplained weight loss beyond expected therapeutic effect, or new onset of constipation after previously tolerating the medication well. Patients over age 50 with new-onset constipation or those with a family history of colorectal cancer should discuss appropriate screening with their provider. Signs of dehydration (extreme thirst, dizziness, dark urine, decreased urination) warrant urgent medical attention.

Patients with pre-existing gastrointestinal conditions such as inflammatory bowel disease, diverticulitis, or previous bowel surgery should maintain closer communication with their healthcare team, as they may be at higher risk for complications.

Healthcare providers can assess whether dose reduction, temporary discontinuation, or alternative weight management strategies are appropriate. They may also investigate other contributing factors such as concurrent medications (opioids, anticholinergics, calcium channel blockers), metabolic abnormalities (hypothyroidism, hypercalcemia), or structural issues. In some cases, referral to a gastroenterologist may be warranted for specialized evaluation and management.

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