Clinical Consequences of Delayed Gastric Emptying With GLP-1 Receptor Agonists and Tirzepatide

• Published in: The journal of clinical endocrinology and metabolism Vol. 110; no. 1; pp. 1 - 15
• Main Authors: Jalleh, Ryan J, Plummer, Mark P, Marathe, Chinmay S, Umapathysivam, Mahesh M, Quast, Daniel R, Rayner, Christopher K, Jones, Karen L, Wu, Tongzhi, Horowitz, Michael, Nauck, Michael A
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 18.12.2024
• Subjects: Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Gastric Emptying - drug effects; Gastric Emptying - physiology; Gastric Inhibitory Polypeptide; Gastroparesis - drug therapy; Glucagon-Like Peptide-1 Receptor Agonists; Glucagon-Like Peptide-2 Receptor; Humans; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Tirzepatide; incretin mimetics; GLP-1 receptor agonists; tachyphylaxis; aspiration; GLP-1/GIP dual receptor agonists; gastric emptying; retained gastric content
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgae719

Abstract Context Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are established therapeutics for type 2 diabetes and obesity. Among other mechanisms, they slow gastric emptying and motility of the small intestine. This helps to limit postprandial glycemic excursions and reduce chylomicron formation and triglyceride absorption. Conversely, motility effects may have detrimental consequences, eg, retained gastric contents at endoscopy or general anesthesia, potentially complicated by pulmonary aspiration or bowel obstruction. Data Acquisition We searched the PubMed database for studies involving GLP-1RA therapy and adverse gastrointestinal/biliary events. Data Synthesis Retained gastric contents at the time of upper gastrointestinal endoscopy are found more frequently with GLP-1 RAs but rarely are associated with pulmonary aspiration. Well-justified recommendations for the periprocedural management of GLP-1RAs (eg, whether to withhold these medications and for how long) are compromised by limited evidence. Important aspects to be considered are (1) their long half-lives, (2) the capacity of GLP-1 receptor agonism to slow gastric emptying even at physiological GLP-1 concentrations, (c) tachyphylaxis observed with prolonged treatment, and (d) the limited effect on gastric emptying in individuals with slow gastric emptying before initiating treatment. Little information is available on the influence of diabetes mellitus itself (ie, in the absence of GLP-1 RA treatment) on retained gastric contents and pulmonary aspiration. Conclusion Prolonged fasting periods regarding solid meal components, point-of-care ultrasound examination for retained gastric content, and the use of prokinetic medications like erythromycin may prove helpful and represent an important area needing further study to increase patient safety for those treated with GLP-1 RAs.