What's Coming Up Next? The Physiology of Gastroparesis and GLP-1 Agonists

Glucagon-like peptide-1 (GLP-1) is an incretin to regulate glycemia, activates peripheral and central neural pathways to control appetite, and inhibits upper gut transit to reduce food intake. Peptide and nonpeptide GLP-1 receptor agonists (GLP-1RAs), as well as a combined GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), agonist are approved for type 2 diabetes, weight reduction, and other indications. GLP-1RA therapy can be complicated by upper gastrointestinal (GI) symptoms, including nausea and vomiting. Delayed gastric emptying secondary to GLP-1RAs may be influenced by drug pharmacokinetics, associated neuropathy, and development of tachyphylaxis with repeated dosing. A theoretical risk of pulmonary aspiration from retained gastric contents is concerning for patients undergoing anesthesia before endoscopy or surgery. Managing upper GI complications of GLP-1RA therapy includes diet modifications, antiemetic medications, and treatments that stimulate gastric emptying. Newer agents in testing include nonpeptide GLP-1RAs and GLP-1RAs acting in concert with GIP, glucagon, or other receptor-mediated pathways.