Does Rybelsus Cause Constipation?
Yes, Rybelsus (oral semaglutide) does cause constipation as a recognized gastrointestinal side effect, though it occurs less frequently than nausea, vomiting, and diarrhea. 1
Incidence and Clinical Evidence
Constipation is documented as a common adverse effect of oral semaglutide across multiple clinical trials:
In Japanese patients with type 2 diabetes, constipation was the most frequently reported gastrointestinal adverse event with oral semaglutide, occurring in 10-13% of patients receiving the medication compared to 6% with placebo 2
The incidence of constipation appears dose-dependent, with higher rates observed at escalating doses (3 mg, 7 mg, and 14 mg) 3
A meta-analysis of randomized controlled trials confirmed that the incidence of constipation with oral semaglutide was higher than placebo 4
Mechanism and Severity
The constipation associated with Rybelsus is primarily related to its GLP-1 receptor agonist mechanism:
GLP-1 receptor agonists delay gastric emptying and slow gastrointestinal motility, which can lead to constipation 1
Most cases are mild to moderate in severity and often transient 2, 3
The gastrointestinal effects, including constipation, are generally most prominent during dose escalation and may improve with continued use 2
Clinical Significance and Safety Concerns
While constipation is typically manageable, severe gastrointestinal complications have been reported:
The American Diabetes Association guidelines specifically warn about "severe constipation and small bowel obstruction/ileus progression" as potential safety concerns with semaglutide 1
These severe complications, though rare, require monitoring for progression beyond typical constipation symptoms 1
Patients already experiencing bloating, nausea, abdominal pain, or discomfort should use caution, as semaglutide may aggravate these symptoms 5
Practical Management Considerations
When prescribing Rybelsus, anticipate and counsel patients about constipation:
Inform patients that constipation is a recognized side effect that occurs in approximately 10-13% of users 2
The effect is generally dose-dependent, so slower titration may reduce severity 3
Most gastrointestinal adverse events are transient and resolve with continued therapy 2, 3
Monitor for progression to severe constipation or signs of bowel obstruction, which would require immediate discontinuation 1