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Review
. 2024 Nov 26;166(1):bqae155.
doi: 10.1210/endocr/bqae155.

Physiology and Pharmacology of Effects of GLP-1-based Therapies on Gastric, Biliary and Intestinal Motility

Ryan J Jalleh  1   2 , Chinmay S Marathe  1   2 , Christopher K Rayner  2   3 , Karen L Jones  1   2 , Mahesh M Umapathysivam  1   2   4 , Tongzhi Wu  2 , Daniel R Quast  5 , Mark P Plummer  2   6 , Michael A Nauck  5   7 , Michael Horowitz  1   2
Affiliations
Review

Physiology and Pharmacology of Effects of GLP-1-based Therapies on Gastric, Biliary and Intestinal Motility

Ryan J Jalleh et al. Endocrinology. .

Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists and the dual GLP-1- and glucose-dependent insulinotropic polypeptide 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 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 (eg, 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.

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Figures

Figure 1.
Figure 1.
Factors that slow or accelerate gastric emptying.
Figure 2.
Figure 2.
Techniques frequently used to measure gastric emptying.
Figure 3.
Figure 3.
Intragastric retention of a 300-mL drink containing 75-g glucose at (A) 120 minutes and (B) 240 minutes after ingestion in 30 participants with T2D after 8 weeks treatment with either lixisenatide 20 µg (n = 15) or placebo (n = 15). Median values are indicated. Lixisenatide substantially slows gastric emptying of liquids at 120 minutes and 240 minutes. Reproduced from Kovoor et al (50). © 2024 The Authors. Published by Elsevier Inc.
Figure 4.
Figure 4.
Mechanisms for the effect of GLP-1/GLP-1RA on gallbladder and gastrointestinal motility.
See this image and copyright information in PMC

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