Zepbound Does Not Cause Colitis
Zepbound (tirzepatide) is not known to cause inflammation in the colon (colitis). There is no evidence in the medical literature or FDA labeling linking tirzepatide to inflammatory bowel disease or colitis.
Key Evidence
What Zepbound Actually Does
- Zepbound is a GLP-1/GIP receptor agonist used for weight loss that primarily affects gastrointestinal motility, not inflammation 1
- The only documented serious GI complication is functional bowel obstruction due to delayed gastric emptying and reduced motility, not inflammatory processes 1
Drugs That Actually Cause Colitis
The following medications have established associations with drug-induced colitis, and tirzepatide is notably absent from this list:
- Immune checkpoint inhibitors (ipilimumab, nivolumab, pembrolizumab) - well-documented cause of immune-mediated colitis 2
- NSAIDs - associated with increased incidence of colonic inflammation 3, 4
- Isotretinoin, antibiotics, oral contraceptives, mycophenolate mofetil, etanercept, rituximab - all implicated in triggering IBD 5
- Vasoconstrictor medications (cocaine, ergots, vasopressin, norepinephrine) - cause ischemic colitis, not inflammatory colitis 3
What the Guidelines Say About Colitis
When evaluating a patient with suspected colitis on CT imaging, the diagnostic workup should focus on:
- Infectious causes first: Stool studies for C. difficile, bacterial pathogens (Salmonella, Shigella, Campylobacter, E. coli), and parasites 4
- Inflammatory markers: Fecal lactoferrin and calprotectin to assess inflammation severity 3, 4
- Endoscopic evaluation: Colonoscopy with biopsies if stool markers elevated or symptoms persist 4
- Specific etiologies: Inflammatory bowel disease, ischemic colitis, immune checkpoint inhibitor colitis, or infection 3, 4
Clinical Pitfalls
Common Misattribution
- Do not confuse delayed gastric emptying with colitis - GLP-1 agonists like Zepbound slow GI transit and can cause constipation, bloating, or functional obstruction, but these are motility issues, not inflammation 1
- CT findings of "colitis" require specific diagnosis - colonic wall thickening on imaging can represent infection, ischemia, or IBD, but requires stool studies and often endoscopy to determine the actual cause 4
What to Actually Monitor
If a patient on Zepbound develops abdominal symptoms:
- Rule out functional obstruction - the documented GI complication of tirzepatide 1
- Evaluate for infectious colitis - perform comprehensive stool workup 4
- Consider ischemic colitis - especially in patients >60 years with cardiovascular comorbidities or on vasoconstrictors 3
- Assess for concurrent IBD - which would be coincidental, not drug-induced
The absence of tirzepatide from all major guidelines on drug-induced colitis 2, 5 and the lack of any case reports linking it to inflammatory colitis strongly supports that Zepbound does not cause colon inflammation.