Holding vs Continuing GLP-1/GIP Agonists Before Upper Endoscopy

Importance: Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are known to increase the risk of retained gastric contents. High-quality data are lacking to guide periprocedure management of GLP-1 and GIP agonists. Objective: To compare the risk of clinically significant residual gastric volume (RGV) in patients who continue vs hold 1 dose of weekly or daily GLP-1 and GIP agonists prior to sedation. Design, Setting, and Participants: This randomized, single-masked clinical trial conducted at 2 large tertiary referral centers in the US included patients undergoing elective upper endoscopy (EGD) who were receiving GLP-1 or GLP-1/GIP agonists between July 2024 and May 2025. Eligible participants were adults aged 18 years or older, scheduled for EGD with or without colonoscopy, under moderate sedation or monitored anesthesia care, and taking a stable dose of a GLP-1 or GLP-1/GIP agonist for at least 1 month. Exclusion criteria were prior foregut surgery, achalasia, documented gastroparesis, RGV on previous endoscopy, gastric outlet obstruction, planned general anesthesia, or recent opioid use. Data were analyzed May 2025. Intervention: Participants were randomized to either continue their medication or hold 1 dose prior to the procedure. Main Outcomes and Measures: Clinically significant RGV, a composite of gastric contents that (1) precludes endoscopic examination, (2) requires premature termination or endotracheal intubation, and/or (3) results in an aspiration event that necessitates extended observation or monitoring, unplanned therapeutics, or hospital admission. Results: There were 60 patients (32 holding 1 dose, 28 continuing medication) in the preplanned interim analysis (median [IQR] age, 62.5 [55.5-67.5] years; 30 female [50.0%]). Clinically significant RGV occurred in 3.1% in the hold group vs 25.0% in the continue group (absolute difference, 21.9% [90% CI, 7.0%-36.7%]; P = .003). The trial was terminated early as risk exceeded the preestablished O'Brien-Fleming stopping boundary. In the EGD-only subgroup (35 patients), clinically significant RGV occurred in 46.7% in the continue vs 5.0% in the hold groups (absolute difference, 41.7% [90% CI, 17.9%-65.4%]; P = .001). In the EGD plus colonoscopy subgroup (25 patients), who were on clear liquids the day prior, no patients had clinically significant RGV. Conclusions and Relevance: This randomized clinical trial found that continuing GLP-1 or GIP agonist in the preprocedural period increased clinically significant RGV but did not increase the risk of other adverse events. Clear liquids the day prior to the procedure may mitigate the risk of clinically significant RGV regardless of GLP-1/GIP use. Trial Registration: ClinicalTrials.gov Identifier: NCT06533527.