Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for the management of type 2 diabetes mellitus and obesity. Their effects on gastric emptying have raised concerns in the perioperative setting, where standard fasting protocols are used to reduce aspiration risk. However, the clinical significance of altered gastric physiology and its implications for perioperative management remain uncertain. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) (registration number: CRD420261289189). A comprehensive literature search identified studies evaluating perioperative gastric physiology and procedural safety outcomes associated with GLP-1 RA use in adults undergoing procedures requiring sedation or general anesthesia. Outcomes included delayed gastric emptying, residual gastric contents, aspiration or regurgitation events, and perioperative management adaptations. Sixteen studies met the inclusion criteria, comprising seven observational studies and nine case reports or case series. Observational evidence demonstrated an association between GLP-1 RA use, particularly semaglutide, and increased residual gastric contents or delayed gastric emptying despite adherence to standard fasting protocols. These findings were identified primarily through gastric ultrasound and endoscopic assessment. In contrast, clinically apparent aspiration or regurgitation events were uncommon and were reported predominantly in case-based literature. Larger observational studies did not demonstrate a clear increase in aspiration or broader perioperative complications. Identification of retained gastric contents also influenced clinical management in several reports, resulting in changes to anesthetic planning, additional gastric assessment, or postponement of elective procedures. GLP-1 RA therapy is associated with alterations in gastric physiology that may challenge the assumptions underlying standard preoperative fasting protocols. Although increased residual gastric contents are consistently reported, current evidence does not establish a corresponding increase in clinically significant aspiration events. Individualized preoperative risk assessment, including consideration of medication exposure and selective use of gastric ultrasound, may assist perioperative decision-making. Further prospective studies are needed to quantify aspiration risk and establish evidence-based perioperative management strategies.
