Physiology and pharmacology of effects of GLP-1 based therapies on gastric, biliary and intestinal motility

Endocrinology. 2024 Nov 21:bqae155. doi: 10.1210/endocr/bqae155. Online ahead of print.

Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and the dual GLP-1 and glucose dependent insulinotropic polypeptide (GIP) receptor co-agonist tirzepatide (referred to here collectively as "GLP-1-based therapy") are incretin-based therapies being used increasingly in the management of both type 2 diabetes (T2D) and obesity. They are now recognized to have beneficial effects beyond improved glycemic control and weight loss, including cardiovascular and renal protection. GLP-1-based therapy also slows gastric emptying, which has benefits (lowering postprandial glucose), but also potential risks (e.g. hypoglycemia in individuals on insulin or sulphonylurea therapy). Their effects on the gallbladder may also be beneficial, contributing to reducing postprandial triglycerides, but they also potentially increase the risk of biliary disease. In this review, we summarize the effects of GLP-1 and incretin-based therapeutics on gastric, biliary and small intestinal function. An improved understanding of these effects will optimize the use of these drugs.

Keywords: biliary; gastric emptying; glucagon-like peptide-1; hypoglycemia; physiology; small intestinal motility.