The global increase in obesity, type 2 diabetes mellitus (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD) has led to a higher use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) among patients undergoing gastrointestinal endoscopy. Although GLP-1RAs provide significant metabolic, cardiovascular, and hepatic benefits, their tendency to slow gastric emptying has raised concerns about retained gastric contents (RGC), procedural complications, and a greater risk of pulmonary aspiration during sedation or anesthesia. This review offers a translational narrative synthesis of mechanistic, physiological, and clinical evidence connecting GLP-1RA therapy to changes in gastric motility and peri-endoscopic outcomes. Data from pharmacological studies, scintigraphic evaluations, large observational cohorts, and international consensus statements are combined to guide physiology-based procedural decisions. Evidence consistently indicates that GLP-1RA exposure is associated with a higher incidence of RGC and more frequent procedural disruptions during upper gastrointestinal endoscopy. However, it remains uncertain whether RGC leads to clinically significant aspiration. Consistent with this, real-world data reveal no increase in aspiration pneumonia among GLP-1RA users undergoing colonoscopy, with reported aspiration rates of approximately 0.01%-0.05%. Likewise, during upper gastrointestinal endoscopy, only a small absolute rise in aspiration-related events has been observed, involving fewer than 0.3% of procedures. Current guidelines favor continuing GLP-1RA therapy alongside dietary modification, structured risk assessment, selective gastric point-of-care ultrasound (POCUS), and multidisciplinary communication, rather than routine cessation. Emerging prospective evidence indicates that implementing a pre-procedural clear liquid diet, with individualized timing of weekly agents, may reduce the risk of clinically significant RGC, complementing existing dietary preparation strategies.
