David Long, DO

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as semaglutide and tirzepatide have exploded in popularity for the treatment of both diabetes mellitus and obesity. As the use of these medications has become more widespread, an obscure side effect has led to significant clinical considerations in the peri-endoscopy arena. Specifically, GLP-1 RAs have been shown to slow gastric emptying and reduce bowel motility due to inhibition of peristalsis at the level of the GLP-1 receptors localized to myenteric neurons.

With this mechanism in mind, the concern for possible adverse events during endoscopy has been explored and validated. The development of gastroparesis in individuals using GLP1-RAs is more than 4 times higher compared to placebo with the clinical implication being an increased rate of retained gastric contents – in fact, a 30% higher prevalence of this was found in GLP-1 RA users.

 Other consequential effects include a 4 times higher likelihood of aborted esophagogastroduodenoscopy and a higher likelihood of suffering from aspiration pneumonia.

 Internal data from the Cleveland Clinic further corroborated these reported findings.

While the motility effects of GLP-1 RAs within the stomach are well known, the remainder of the bowel is not immune to experiencing the same phenomenon resulting in motility consequences downstream. One such example is the significant negative impact these medications have on the quality of bowel preparation for colonoscopy.

 After studying our own internal data here at Cleveland Clinic, similar findings were observed with poor bowel preparation rates being significantly higher in those using GLP-1 RAs.

Taking the study a step further, the clinical significance was examined by comparing both adenoma detection rates and sessile serrated polyp (SSP) detection rates between users and non-users. Fortunately, adenoma detection rates were unaffected by GLP-1 RA use despite worse bowel preparation. However, SSP detection rates were significantly lower in GLP-1 RA users when compared with nonusers, suggesting GLP-1 RA use is associated with a lower-quality colon cancer screening exam.

Given these adverse effects, the American Society of Anesthesiologists has made recommendations for peri-endoscopic management of GLP-1 RA use that have largely been adopted by hospitals nationwide. These recommendations suggest holding the medication prior to the planned procedure at an interval dependent on the half-life of the medication. For example, long-acting formulations are recommended to be held for 1 week prior to upper endoscopy to reduce the risk of aspiration. This recommended hold period is roughly equivalent to a single half-life of a typical long-acting GLP-1 RAs.

It is unclear if this is enough to ameliorate the effects of decreased motility and consequential increase of retained gastric contents. A more practical approach was recently described in an American Gastroenterological Association Rapid Clinical Practice Update recommending a liquid diet the day prior to upper endoscopy in patients using GLP-1 RAs in lieu of holding the medication. There remains no guidance for colonoscopy bowel preparation strategies to address the poor preps often observed in patients actively using GLP-1 RAs.

While the popularity of GLP-1 RAs only recently exploded, the ill effects on endoscopy are coming to light. More studies are needed to understand which approaches to endoscopy and colonoscopy are most effective in reducing potential harm for our patients while ensuring they receive a high-quality endoscopic exam.

Sodhi M, Rezaeianzadeh R, Kezouh A, et al. Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss. 

 2023;330(18):1795–1797. doi:10.1001/jama.2023.19574

Sen S, Potnuru PP, Hernandez N, et al. Glucagon-Like Peptide-1 Receptor Agonist Use and Residual Gastric Content Before Anesthesia. 

 2024;159(6):660–667. doi:10.1001/jamasurg.2024.0111

Nadeem D, Taye M, Still MD, et al. Effects of glucagon-like peptide-1 receptor agonists on upper endoscopy in diabetic and nondiabetic patients. 

Yeo YH, Gaddam S, Ng WH, et al. Increased Risk of Aspiration Pneumonia Associated With Endoscopic Procedures Among Patients With Glucagon-like Peptide 1 Receptor Agonist Use. 

. 2024;167(2):402-404.e3. doi:10.1053/j.gastro.2024.03.015

Firkins SA, Yates J, Shukla N, et al. Clinical Outcomes and Safety of Upper Endoscopy While on Glucagon-Like Peptide-1 Receptor Agonists. 

Yao R, Gala KS, Ghusn W, et al. Effect of Glucagon-Like Peptide-1 Receptor Agonists on Bowel Preparation for Colonoscopy. 

. 2024;119(6):1154-1157. doi:10.14309/ajg.0000000000002564

Articles

With the growing popularity of GLP-1 receptor agonists, understanding their impact on gastric emptying, bowel motility, and potential implications for endoscopy is essential.