Gastric Emptying
The process by which food moves from the stomach into the small intestine. GLP-1 receptor agonists slow gastric emptying, which reduces postprandial glucose spikes and prolongs satiety. This mechanism also underlies common gastrointestinal side effects and potential drug interactions.
Technical Context
Gastric emptying rate is regulated by: duodenal nutrient feedback (fat and acid slow emptying via CCK and secretin), hormonal signals (GLP-1, PYY, amylin slow emptying; ghrelin, motilin accelerate), vagal tone (parasympathetic stimulation promotes emptying), and intrinsic gastric motility (antral contractions, pyloric relaxation). GLP-1 RAs slow gastric emptying dose-dependently, primarily through inhibition of vagal efferent output to gastric smooth muscle. Tachyphylaxis: the gastric emptying delay attenuates with chronic GLP-1 RA use — short-acting agents (exenatide BID, lixisenatide) cause more pronounced meal-by-meal slowing (because they provide intermittent receptor activation), while long-acting agents (semaglutide, dulaglutide) cause less gastric emptying delay at steady state due to continuous receptor activation and subsequent adaptation. This tachyphylaxis explains why long-acting GLP-1 RAs have relatively greater effects on fasting glucose (via glucagon suppression) than postprandial glucose.