GLP-1 Receptor Agonists and Gastroparesis

Mechanism of Action

GLP-1 receptor agonists delay gastric emptying through vagal nerve-mediated pathways, which can exacerbate pre-existing gastroparesis, by reducing phasic gastric contractions, delaying gastric emptying, reducing gastric acid secretion, and increasing both fasting and postprandial gastric volumes 1
The delay in gastric emptying is a key mechanism of action for GLP-1 receptor agonists, which contributes to their glucose-lowering and weight loss effects 1

The American Gastroenterological Association (AGA) lists GLP-1 receptor agonists as a potential cause of gastroparesis in their clinical practice update 2
Multiple guidelines highlight that GLP-1 receptor agonists frequently cause delayed gastric emptying, which would worsen pre-existing gastroparesis 3, 4
Clinical practice recommendations advise documenting symptoms of nausea, vomiting, or abdominal distention in patients taking GLP-1 receptor agonists, which are common symptoms of gastroparesis 3

Short-acting GLP-1 receptor agonists (like exenatide) have more pronounced effects on delaying gastric emptying than long-acting formulations 1
There is evidence of tachyphylaxis (diminishing effect over time) with continuous exposure to GLP-1 receptor agonists, suggesting adaptation of the autonomic nervous system 1, 5
Despite potential tachyphylaxis, recent studies question whether this adaptation is clinically significant in the perioperative setting 6

For patients who must use GLP-1 receptor agonists despite risk factors, starting at low doses and titrating upward slowly can help minimize gastrointestinal side effects 1
Reducing meal size and avoiding high-fat diets can help manage GI symptoms in patients taking GLP-1 receptor agonists 1
Consideration of evaluation with appropriate motility testing, such as scintigraphy, rather than less reliable methods, is recommended for patients at risk 1

For patients taking GLP-1 receptor agonists for weight management, withhold these drugs for at least three half-lives before elective surgical procedures, as recommended by the Anaesthesia guideline society 7, 8
For patients with type 2 diabetes, prolonged cessation before surgery may have detrimental effects on perioperative glycemic control, and discussion with an endocrinologist is advised, according to the Anaesthesia guideline society 7, 8