Introduction:
Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide, have efficacious results for enhancing glycemic control, promoting weight loss, and reducing cardiovascular risk leading to their increased utilization. As they affect hormone-mediated pathways, there are increasing concerns GLP-1RAs can affect gastric retention of food contents and thereby elevate the risk of anesthesia-related complications. Given this, recent consensus recommendations suggest pausing GLP-1RAs pre-procedure based on half-life, acknowledging limited data. This study investigated gastric food retention and endoscopic outcomes in patients on semaglutide undergoing anterograde endoscopic procedures.

Methods:
A retrospective cohort of adult patients at a tertiary care center undergoing anterograde endoscopic procedures between January 2021 to July 2023 was conducted. Patients with malignancy-related gastric outlet obstruction were excluded. Demographic and clinical data such as age, gender, GLP-1RA usage at procedure time, procedure indication, and same-day colonoscopy during anterograde endoscopic assessment were recorded. Propensity score matching was used to control for confounding factors by balancing measured baseline confounders and risk factors. Multivariate logistic regression assessed the relationship between semaglutide use and gastric food retention.

Results:
2646 patients underwent anterograde endoscopic procedures with 218 (8.2%) patients on GLP1RAs. Endoscopy was performed for the following indications: heartburn and dyspepsia (37.2%, n=985), gastrointestinal bleeding (22.5%, n=595), abdominal pain (12.5%, n=329), nausea and vomiting (2.5%, n=67), or other indication (25.3%, n=670). Endoscopic evaluation revealed that 10.9% (n=289) of the cohort had retained gastric food contents.

Semaglutide users showed notably higher retained gastric food content rates than non-users (31.2% vs. 9.1%, p<0.001). Propensity-matched analysis confirmed an association between semaglutide use and increased stomach food retention (p<0.05). Semaglutide users undergoing endoscopy for related symptoms (heartburn, dyspepsia, abdominal pain, nausea, vomiting) were 71% more likely to have gastric food retention when compared with those undergoing endoscopy for GI bleeding or other indications (p<0.001). Interestingly, same-day colonoscopy reduced the risk of gastric food retention (p<0.001).

Conclusion:
Semaglutide use was found to increase rates of retained stomach contents during endoscopic procedures. The protective effect of same-day colonoscopy demonstrates the relevance of pre-procedural fasting protocols in procedural outcomes and mitigation of gastric food retention rates for GLP-1RA users. Further studies are needed to clarify how GLP-1RA medications, procedural outcomes, and fasting protocols interact and to develop clinical guidelines for this patient group.

<sup>1</sup>Values expressed as mean (percentile 25, 75%); <sup>2</sup>Values expressed as %(n). P-values are t-test or chi-square test as appropriate for continuous and categorical variables, respectively. <sup>†</sup>Symptoms represent “abdominal pain / heartburn & dyspepsia / nausea & vomiting”.

¹Values expressed as mean (percentile 25, 75%); ²Values expressed as %(n). P-values are t-test or chi-square test as appropriate for continuous and categorical variables, respectively. ^†Symptoms represent “abdominal pain / heartburn & dyspepsia / nausea & vomiting”.

Estimates correspond to odds ratio (OR). CI = confidence interval. (A) Matched control analysis including semaglutide use and presence of several types of indication, separately. ¹Values expressed as mean (percentile 25%, 75%); ²Values expressed as % (n). ³P-values are based on univariable logistic regression model, using propensity score matching weights. ⁴P-values are based on multivariable logistic regression model, using propensity score matching weights. ^†Symptoms represent “abdominal pain/heartburn & dyspepsia/nausea & vomiting”.

Ariel Gonzalez

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