Discontinuation Recommendations for GLP-1 Receptor Agonists Prior to Colonoscopy: A Randomized Controlled Trial in Taiwan.

Background： Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become increasingly prevalent in modern clinical practice, extending their therapeutic roles beyond glycemic control in type 2 diabetes mellitus (T2DM) to encompass weight management, cardiovascular protection, and emerging indications in hepatic diseases. The growing adoption of GLP-1 RAs, including newer agents such as tirzepatide, has highlighted their beneficial effects on metabolic health. However, their pharmacological action of delaying gastric emptying and suppressing gastrointestinal motility has raised concerns regarding their potential impact on bowel preparation quality prior to colonoscopy.

Colonoscopy remains a cornerstone modality for colorectal cancer screening and prevention, where high-quality bowel preparation is essential for adequate mucosal visualization and lesion detection. Inadequate bowel preparation not only compromises diagnostic accuracy but also increases the risk of missed lesions, procedural complications, and necessitates repeat examinations, leading to greater healthcare costs and patient burden. Current guidelines advocate split-dose polyethylene glycol (PEG)-based regimens as the standard for bowel cleansing; however, patient-related factors, including the use of medications that inhibit gastrointestinal motility, are recognized contributors to bowel preparation failure.

GLP-1 RAs are classified as enterogastrones, exerting their effects via the ileal brake mechanism, which slows upper gastrointestinal transit in response to nutrient exposure. While this effect is therapeutically advantageous for glycemic control and weight reduction, it may inadvertently impair bowel cleansing efficacy. Preliminary evidence suggests that GLP-1 RA users are at higher risk of inadequate bowel preparation and repeat colonoscopy. Nonetheless, empirical data regarding optimal peri-procedural management, specifically the appropriate discontinuation interval of GLP-1 RAs prior to colonoscopy, remain scarce.

Given the pharmacokinetic diversity of GLP-1 RAs and their prolonged half-lives, it is unclear how long prior to colonoscopy these agents should be withheld to mitigate their gastrointestinal motility-suppressing effects and reduce the likelihood of suboptimal bowel cleansing. The absence of evidence-based discontinuation guidelines for GLP-1 RAs in this setting represents an unmet clinical need.

This study aims to evaluate the relationship between GLP-1 RA discontinuation intervals and bowel preparation adequacy, Using BBPS(Boston Bowel Preparation Scale) as a surrogate marker for inadequate bowel cleansing. By determining the optimal discontinuation timeframe for GLP-1 RAs, we seek to provide clinically actionable recommendations to optimize colonoscopy outcomes in this growing patient population.

Inclusion criteria

• Inclusion Criteria for non GLP-1 user:

• Individuals who are scheduled to undergo total colonoscopy for any reasons
• Age between 18 to 70 years.
• ECOG Performance status is 0 or 1.
• Written consent to participate in the study has been obtained.
• Outpatient department patient
• Stop at least 3 days if current using medications that promote or inhibit gastrointestinal motility.

Exclusion criteria

• • Presence of severe comorbid conditions that preclude the safe performance of colonoscopy (e.g., unstable angina, recent myocardial infarction, decompensated heart failure, chronic respiratory disease, or bleeding diathesis).

• History of prior gastric, small bowel, or colorectal segmental resection (patients with isolated appendectomy are eligible).
• Family history of hereditary colorectal cancer syndromes.
• Current or prior diagnosis of inflammatory bowel disease.
• Known colorectal polyposis syndromes.
• Any other condition deemed inappropriate for study participation at the discretion of the treating physician.
• Body mass index (BMI) > 40 kg/m².
• Diagnosis of liver cirrhosis.
• Diagnosis of Parkinson's disease.
• Diagnosis of dementia.
• Use of tricyclic antidepressants or opioid medications for more than 3 months.