With the growing use of GLP-1 receptor agonists such as Rybelsus® (oral semaglutide) for type 2 diabetes and weight management, clinicians are increasingly faced with questions regarding their safe use around elective procedures, particularly colonoscopy. These agents offer significant metabolic and cardiovascular benefits but are also known to delay gastric emptying, a mechanism that, while therapeutic, raises procedural concerns.
In the context of sedation-based procedures, delayed gastric transit has prompted fears of incomplete fasting, aspiration risk, and impaired bowel preparation, particularly in patients reporting nausea, early satiety, or signs of gastroparesis. Until recently, practice varied widely, with many providers opting to withhold GLP-1 medications before endoscopy despite limited data and inconsistent recommendations.
In 2024, a consortium of medical societies issued updated, harmonized guidance clarifying when discontinuation is necessary and when it is not. For most patients undergoing colonoscopy, routine cessation of GLP-1 therapy, including oral semaglutide, is no longer advised. However, certain clinical scenarios still warrant caution.
This article outlines the pathophysiologic rationale, summarizes the new guidance, and offers practical strategies for bowel prep, medication management, and decision-making in the endoscopy suite.
Background: Risk of Aspiration Due to Delayed Gastric Emptying
GLP-1 receptor agonists, including semaglutide, delay gastric emptying by reducing gastric motility and altering vagal tone. This effect contributes to improved postprandial glycemic control and weight loss, but it may also result in residual gastric contents during procedures performed under sedation.
Though colonoscopy is typically low-risk for aspiration compared to upper endoscopy or surgery under general anesthesia, there remains concern that incomplete gastric emptying could complicate sedation safety, especially in patients reporting nausea, early satiety, or symptoms consistent with gastroparesis. Additionally, reduced motility may impair bowel preparation, increasing the risk of inadequate visualization.
Prior to 2024, in the absence of consensus guidelines, many clinicians erred on the side of caution, advising temporary discontinuation of GLP-1 agents before endoscopic procedures. This approach, however, was not evidence-based and may have led to unnecessary therapy interruptions.
New Multi-Society Guidelines (2024)
In response to growing clinical uncertainty, multiple professional societies, including the American Society of Anesthesiologists (ASA), American Gastroenterological Association (AGA), and American Society for Gastrointestinal Endoscopy (ASGE), issued joint guidance in 2024 addressing the peri-procedural management of GLP-1 receptor agonists (Reuters, 2024).
The consensus statement clarifies that for most patients undergoing routine colonoscopy, GLP-1 agonists, including oral semaglutide (Rybelsus), do not need to be discontinued. Standard bowel prep and fasting protocols are sufficient to ensure procedural safety in individuals without significant gastrointestinal symptoms.
However, exceptions apply. Temporary withholding is still recommended for patients with documented or suspected gastroparesis, persistent nausea or vomiting, or those scheduled for upper endoscopy or procedures requiring deep sedation or general anesthesia. This shift toward a risk-based approach reflects a growing understanding of GLP-1 pharmacodynamics and aims to reduce unwarranted medication interruptions, which can destabilize glycemic control and weight management in vulnerable patients.
24-Hour Liquid Diet and Split-Dose Prep
For patients on GLP-1 receptor agonists such as Rybelsus, modifications to the standard bowel preparation protocol may improve tolerability and procedural success. A 2024 update from Digestive Disease Week (DDW) emphasized that individualizing prep based on satiety and GI symptoms is essential for achieving adequate colon visualization (DDW News, 2024). A 24-hour clear liquid diet is increasingly recommended for patients who experience early satiety or delayed gastric transit, both of which may be exacerbated by GLP-1 therapy. In addition, a split-dose polyethylene glycol (PEG) regimen, with the second dose taken 4–6 hours before the procedure, has shown superior cleansing and lower nausea compared to traditional single-dose regimens.
Patients should be advised to avoid fatty or high-fiber foods the day before the procedure and to maintain aggressive hydration throughout. Because semaglutide can blunt thirst perception, active reminders to drink fluids, within prep guidelines, are important to ensure complete evacuation and patient comfort.
Should Rybelsus Be Discontinued Before the Procedure?
In most cases, discontinuation of Rybelsus before colonoscopy is not required, provided the patient adheres to standard fasting and bowel prep protocols. However, temporary interruption may be warranted for individuals with gastroparesis, persistent nausea, or poor prep tolerance. If symptoms are present, clinicians may advise holding Rybelsus the day before and the day of the procedure. Therapy can typically be resumed the morning after colonoscopy, once oral intake is tolerated.
Clinical discretion remains key. For complex cases, coordination between gastroenterology, endocrinology, and anesthesia teams ensures both procedural safety and ongoing metabolic control.
Algorithm for the Endoscopy Room
A structured, symptom- and risk-based approach is essential for managing patients taking Rybelsus (oral semaglutide) who present for colonoscopy. The following checklist can assist procedural teams in ensuring both patient safety and procedure success:
- Confirm last Rybelsus dose and timing of ingestion, particularly if taken within 24 hours.
- Verify bowel preparation completion and quality of evacuation, ideally documented by the patient or nursing team.
- Screen for upper GI symptoms, including nausea, vomiting, early satiety, or signs suggestive of gastroparesis.
- Assess aspiration risk, considering the sedation plan (e.g., moderate vs. deep sedation), patient comorbidities, and prep tolerance.
- Evaluate hydration status, as GLP-1 agonists may reduce thirst perception, contributing to underhydration during bowel prep.
For patients with no active GI symptoms, adequate prep, and low aspiration risk, colonoscopy can proceed under standard protocols. In contrast, if concerns arise, such as incomplete prep, ongoing nausea, or symptoms of delayed gastric emptying, clinicians should pause and consider anesthesia consultation or procedure rescheduling.
Post-procedure, it is important to document GLP-1 receptor agonist use in the endoscopy report and provide clear instructions on when to resume Rybelsus. In most cases, resumption is safe once the patient has tolerated solid oral intake without GI symptoms.
Endoscopy teams should maintain awareness of GLP-1-related effects on gastric motility and hydration, which can subtly impair prep quality or post-procedural recovery if not addressed preemptively.