Semaglutide and Risk of Ischemic Colitis
Based on current evidence, there is no established association between semaglutide and increased risk of ischemic colitis in the major cardiovascular outcome trials, though gastrointestinal side effects are common and there is a recent case report suggesting a potential link that warrants monitoring.
Evidence from Major Clinical Trials
Semaglutide has been extensively studied in large cardiovascular outcome trials including SUSTAIN-6 and PIONEER-6, with no specific signal for ischemic colitis reported in these major studies 1.
The most commonly reported gastrointestinal adverse effects of semaglutide are nausea, vomiting, diarrhea, and constipation, which are typically mild to moderate and transient 2.
In the SUSTAIN-6 trial, more patients discontinued treatment in the semaglutide group due to adverse events, primarily gastrointestinal in nature, but ischemic colitis was not specifically identified as a concern 1.
Gastrointestinal Effects of Semaglutide
Semaglutide, like other GLP-1 receptor agonists, slows gastric emptying, which can lead to various gastrointestinal symptoms 1.
Recent observational studies have shown that patients on GLP-1 receptor agonists, including semaglutide, have higher rates of retained gastric contents even after prolonged fasting periods 1.
Gastrointestinal disorders including severe constipation and small bowel obstruction/ileus progression have been reported with semaglutide use, which theoretically could affect colonic blood flow 1.
Recent Case Report and Potential Mechanism
A recent case report (2025) described a 43-year-old female patient who developed ischemic colitis while on semaglutide (Ozempic) without traditional risk factors for the condition. Her symptoms resolved after discontinuation of the medication 3.
The mechanism by which semaglutide could potentially contribute to ischemic colitis is not established, but may relate to:
Risk Factors for Ischemic Colitis
Traditional risk factors for ischemic colitis include advanced age, cardiovascular disease, constipation, and certain medications including calcium channel antagonists 4.
Constipation, which can be exacerbated by semaglutide, is an independent risk factor for ischemic colitis in young and middle-aged adults 4.
Ischemic colitis accounts for approximately 1 in 1000 hospitalizations, though its incidence is likely underestimated due to mild and transient presentations 5.
Clinical Implications and Monitoring
Patients taking semaglutide who develop severe abdominal pain, particularly left-sided, accompanied by bloody diarrhea should be evaluated for possible ischemic colitis 5, 3.
Patients with existing risk factors for ischemic colitis (cardiovascular disease, constipation, use of vasoconstrictive medications) may warrant closer monitoring when initiating semaglutide therapy 4.
The overall safety profile of semaglutide remains favorable, with cardiovascular benefits demonstrated in multiple large trials 1, 2.
Conclusion
While there is a single case report suggesting a potential association between semaglutide and ischemic colitis, this has not been identified as a significant safety concern in large clinical trials. However, clinicians should be aware of this potential rare complication, particularly in patients with existing risk factors for ischemic colitis or those who develop concerning gastrointestinal symptoms while on therapy.