Medically authored by Joshua Silva, MD | Evidence-Based Weight Loss at Potere Health MD

Quick Answer

Is diarrhea normal on Wegovy® or Zepbound®?

Yes. Diarrhea is a common side effect of GLP-1 and GLP-1/GIP medications such as semaglutide and tirzepatide, particularly during early treatment or dose increases. In most patients it is mild and temporary, reflecting medication-related changes in gastrointestinal motility rather than intestinal injury. Persistent symptoms or warning signs should prompt medical evaluation.¹–³

On GLP-1 medications, diarrhea and constipation are usually motility-related effects, not signs of bowel damage, and the timing around dose changes is often the key clue.

What to do first: focus on smaller meals, adequate hydration, and staying at a stable dose rather than skipping injections.

Call your provider sooner rather than later if diarrhea lasts more than 3 days, limits fluid intake, or is accompanied by severe pain, fever, or blood in the stool.

When Bowel Changes Typically Occur on GLP-1 Therapy

Across clinical trials and post-marketing experience, gastrointestinal side effects from GLP-1–based medications are most common during initiation and dose escalation, not during long-term maintenance therapy.¹–⁴

Patients most often notice bowel changes:

Patients most often notice bowel changes:

• In the first 4–8 weeks of treatment

• Briefly after dose increases

• Less commonly once a dose is held stable

• After certain foods, including large meals, spicy foods, alcohol, or a sudden increase in high-fiber or bulky foods (such as legumes, large salads, raw cruciferous vegetables, or popcorn)

Clinical context: The timing and pattern of symptoms are often more informative than stool appearance alone.

Why GLP-1 Medications Affect Bowel Habits

Proposed mechanisms — not physiologic absolutes

GLP-1 receptor agonists act throughout the gastrointestinal tract. While delayed gastric emptying explains early nausea and fullness, lower-GI symptoms such as diarrhea or constipation reflect more complex and variable physiology that differs between individuals.⁵–⁷

1) Altered Gastrointestinal Motility (“Motility Mismatch” Hypothesis)

Medical framing: GLP-1 receptor agonists activate the ileal brake, slowing gastric emptying. At the same time, GLP-1 receptors are expressed in the enteric nervous system and myenteric plexus, and experimental data suggest GLP-1 signaling may increase colonic peristalsis in some contexts.⁶–⁹

Plain-language translation: Food may leave the stomach slowly but move through the colon more quickly, leading to loose stools once digestion catches up.

This represents a proposed, patient-specific mechanism, not a universal or predictable effect.

2) Fat-Sensitive Osmotic Effects

Medical framing: Delayed gastric emptying may desynchronize nutrient delivery with bile and pancreatic enzyme secretion. When high-fat meals are incompletely processed, unabsorbed fatty acids reaching the colon can exert an osmotic and secretory effect, increasing stool water content.¹⁰–¹¹

Plain-language translation: Greasy or rich foods are more likely to trigger diarrhea early in treatment—not because fat is inherently harmful, but because digestion timing is temporarily altered.

3) Volume & Fermentation Sensitivity (“The Salad Paradox”)

Medical framing: Because GLP-1 medications delay gastric emptying, large-volume or highly fibrous foods—particularly those rich in fermentable carbohydrates—may remain in the stomach longer than usual. When these foods reach the intestines partially digested, rapid bacterial fermentation can produce gas and increase luminal water content, contributing to bloating and loose stools.⁵,⁷,¹⁰

Plain-language translation: “Healthy” foods like large raw salads, broccoli, cauliflower, or kale can sometimes cause as much trouble as greasy foods. Cooked vegetables and smaller portions are often better tolerated during GLP-1 dose adjustments.

4) Constipation-Related Overflow Diarrhea (Commonly Missed)

This is one of the most commonly misinterpreted bowel side effects on GLP-1 therapy—and a reason anti-diarrheal medications can sometimes worsen symptoms.

Medical framing: GLP-1–associated constipation can lead to fecal retention in the distal colon or rectum, allowing liquid stool from upstream to bypass hardened stool and present as diarrhea.¹²–¹³

Plain-language translation: Some patients appear to have diarrhea, but the underlying issue is actually constipation causing liquid stool to leak around harder stool.

Clinical pearl: Small-volume, frequent watery stools accompanied by bloating or a sense of incomplete emptying should prompt evaluation for constipation or fecal impaction before using anti-diarrheal medications.¹²–¹⁴

🔗 Related: Constipation on GLP-1 Medications: A Step-by-Step MD Fix (Fiber, Laxatives, and Red Flags)

5) Microbiome and Transit-Time Changes (Less Common)

Medical framing: Altered intestinal transit time may influence gut microbial composition in some patients, potentially contributing to bloating and intermittent diarrhea.¹⁵–¹⁶

Plain-language translation: In a minority of patients, temporary shifts in gut bacteria may play a role.

This is not the typical cause and should not be assumed without evaluation.

How Long Does Diarrhea Last on Semaglutide or Tirzepatide?

Most patients who experience diarrhea related to GLP-1 therapy improve within 2–4 weeks once a dose is held stable.¹–³ Brief recurrence during dose escalation is common. Persistent diarrhea is not expected and deserves assessment.

Why Diarrhea Matters More on GLP-1s: Dehydration & Kidney Risk

Diarrhea on GLP-1 therapy is usually benign, but it matters clinically because volume depletion can occur—especially when diarrhea is combined with nausea, vomiting, or reduced oral intake.¹⁵–¹⁶

Reports of acute kidney injury associated with GLP-1 receptor agonists are most often linked to dehydration, not direct kidney toxicity.¹⁵–¹⁶

Clinical takeaway: Persistent diarrhea should not be ignored—not because it is dangerous by itself, but because dehydration can escalate quickly if intake is limited.

🔗 Related (upcoming): Dehydration & Kidney Risk on GLP-1s: The Electrolyte + Fluid Plan

What to Do First (Evidence-Aligned, Non-Prescriptive)

Eating Pattern Adjustments

• Smaller, more frequent meals

• Temporarily reduce high-fat or very rich foods, especially during dose changes

• Favor bland, low-irritant foods during flares, such as:

  • Eggs, yogurt, cottage cheese

  • Rice, oatmeal, toast, potatoes

  • Lean proteins and cooked vegetables

• If you know you’re sensitive, temporarily limit bulky or high-fermentation foods, including:

  • Large raw salads

  • Raw cruciferous vegetables (broccoli, cauliflower, cabbage)

  • Legumes, popcorn, or very high-fiber meals

(Rigid “BRAT diet” prescriptions are unnecessary for most patients.)

Hydration Awareness

• Maintain fluid intake if stool frequency increases

• Worsening diarrhea combined with poor intake is a reason to call early

A detailed electrolyte strategy is addressed separately.

Dose Adjustment Strategies (Clinician-Guided)

Gastrointestinal side effects on GLP-1 therapy are often dose-related, particularly during escalation. When diarrhea is persistent or disruptive, clinicians may consider temporary dose adjustments rather than discontinuing therapy altogether.

Common clinician-guided strategies include:

• Staying at the current dose longer before increasing, allowing the gut more time to adapt

• Temporarily reducing the dose, then re-advancing more slowly once symptoms improve

• Dividing the weekly dose into smaller, more frequent injections (when clinically appropriate and feasible) to improve tolerability

Clinical context: Needing additional time or a slower titration does not mean the medication “isn’t working.” Many patients tolerate GLP-1 therapy well long-term once dosing is individualized.

Medications — What Helps and What Requires Caution

Loperamide (Imodium®)

Loperamide may help short-term, non-bloody, afebrile diarrhea. It should be avoided or used cautiously if there is severe abdominal pain, fever, blood in the stool, or concern for constipation or fecal retention.¹⁴

Soluble Fiber (e.g., Psyllium)

Soluble fiber can help absorb excess water and bulk loose stool. This may seem counterintuitive because fiber is often recommended for constipation. However, soluble fiber works differently than insoluble fiber—it forms a gel that can normalize stool consistency in either direction, helping both loose stools and constipation depending on the situation.

Prescription Therapies (Clinician-Guided, Select Cases)

In rare cases where diarrhea is persistent, severe, or unresponsive to dose adjustment and dietary changes, clinicians may evaluate for other contributing factors such as bile acid malabsorption. In these situations, prescription therapies (such as bile acid sequestrants) may be considered under medical supervision.

Clinical context:If prescription anti-diarrheal therapy is required to tolerate GLP-1 treatment, it may be appropriate to reassess the overall risk–benefit balance of continuing the medication.

When Diarrhea May Not Be From the GLP-1

Not every episode of diarrhea during GLP-1 therapy is medication-related. Other common causes include viral gastroenteritis, new medications (such as metformin or magnesium supplements), sugar alcohols (found in some artificial sweeteners), or abrupt dietary changes.¹⁷–¹⁸

🚩 Red Flags — When to Call the Clinic or Seek Care

Contact your clinician promptly if you experience:

• Diarrhea lasting more than 3 days

• Inability to maintain hydration

• Dizziness, minimal urination, or dark urine

• Severe or worsening abdominal pain

• Fever

• Black or bloody stools

• “Leaking” liquid stool with bloating or rectal pressure (possible overflow diarrhea)

Should You Skip or Stop Your GLP-1 Dose?

Do not stop or adjust your GLP-1 medication without guidance. Skipping doses or stopping and restarting can prevent the body from adapting to the medication, which is often what allows gastrointestinal side effects to improve over time.

Persistent symptoms may indicate that dose escalation was too rapid or that additional stabilization time is needed. Any dose changes should be clinician-guided.¹⁵

How This Relates to Other GLP-1 Side-Effect Topics

Constipation: requires a separate, structured plan

• 🔗 Constipation on GLP-1 Medications: A Step-by-Step MD Fix (Fiber, Laxatives, and Red Flags)

Muscle loss: inadequate intake during GI symptoms may worsen lean mass loss

• 🔗 GLP-1 & Muscle Loss

Dehydration & kidney safety: addressed in depth separately

• 🔗 Dehydration & Kidney Risk on GLP-1s: The Electrolyte + Fluid Plan (upcoming)

Frequently Asked Questions

Can GLP-1 medications cause both constipation and diarrhea in the same person?

Yes. Because GLP-1 medications alter gut motility and digestion, some patients experience constipation at one stage and diarrhea at another, particularly during dose changes. The timing and pattern help determine the cause.

Is diarrhea normal on Wegovy® or Zepbound®?

Yes—especially early in treatment or during dose increases.

How long does it usually last?

Most patients improve within a few weeks at a stable dose.

What should I do about my GLP-1 dose if I have diarrhea?

Do not skip or stop doses on your own. Skipping doses or stopping and restarting can interfere with the body’s ability to adapt, which is often what allows side effects to improve. Persistent symptoms should be discussed with your clinician.

What foods help?

Smaller meals and temporarily reducing high-fat or bulky foods often help.

When should I worry?

Persistent symptoms, dehydration, severe pain, fever, or blood in the stool warrant medical evaluation.

Disclaimer

This article is for educational purposes only and is not a substitute for medical advice.

About the Author

Dr. Joshua Silva, MD, is a licensed physician and Medical Director of Potere Health MD. He earned his medical degree from the University of Hawaiʻi John A. Burns School of Medicine and completed residency training in Occupational and Environmental Medicine at the University of Utah, where he also earned a master’s degree in Occupational Health. He later completed a Master of Business Administration with an emphasis in health care administration at Ohio University.

Dr. Silva specializes in evidence-based weight management, including the expert management of diarrhea and other GI side effects common with GLP-1 and GIP therapies such as semaglutide and tirzepatide. He provides in-person and virtual care for patients in Salt Lake City, St. George, and Cedar City, Utah.

References

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