Complications in the Epigastric Region When Using GLP-1 Receptor Agonists

Common Epigastric Complications

Nausea and vomiting are dose-dependent and occur more frequently with short-acting than long-acting GLP-1 receptor agonists, significantly impacting patient quality of life 1, 2
Dyspepsia is a common epigastric discomfort that can persist during treatment with GLP-1 receptor agonists 3, 2
Gastroesophageal reflux can develop as GLP-1 receptor agonists delay gastric emptying 2
Acute pancreatitis is a rare but serious complication linked particularly to exenatide use, with the American Association of Clinical Endocrinologists recommending caution in patients with a history of pancreatitis 4

Delayed gastric emptying is a primary mechanism by which GLP-1 receptor agonists cause epigastric symptoms, leading to prolonged gastric retention 5, 6
Central effects on appetite regulation, through action on the arcuate nucleus in the hypothalamus and the area postrema and nucleus tractus solitarius in the medulla, affect satiety signals and contribute to gastrointestinal symptoms 3
Effects on vagal nerve endings, with receptors on the afferent vagal nerve endings in the intestinal mucosa, generate signals that can contribute to gastrointestinal symptoms 3

The American Association of Clinical Endocrinologists recommends using GLP-1 receptor agonists with caution in patients with a history of pancreatitis, due to the increased risk of acute pancreatitis 4
GLP-1 receptor agonists may increase the risk of gallbladder disease, including acute cholecystitis, with the FDA reporting cholelithiasis and cholecystitis in patients using liraglutide 7

Starting at a low dose and titrating slowly can help improve gastrointestinal tolerability, according to the American College of Cardiology 1, 2
Reducing meal size, limiting alcohol and carbonated drinks, and avoiding high-fat diets may help minimize symptoms 2
Avoiding GLP-1 receptor agonists in patients with pre-existing gastroparesis and monitoring for pancreatitis, especially in patients with risk factors, are crucial management strategies 2, 4

Temporary discontinuation of GLP-1 receptor agonists before elective surgery requiring general anesthesia may be necessary due to the risk of pulmonary aspiration, as recommended by the American College of Cardiology 5
Concomitant medications may have their absorption affected due to delayed gastric emptying, with the American Heart Association recommending caution when using GLP-1 receptor agonists with other oral medications 7, 8

The American College of Cardiology recommends that gastrointestinal symptoms of GLP-1 RAs, such as nausea and vomiting, can be mitigated by gradual dose escalation, which is usually transient for longer-acting GLP-1 RAs 9
GLP-1 RAs have been shown to reduce the risk of major adverse cardiovascular events in people with diabetes mellitus, and can improve surrogate markers of cardiovascular disease in people with and without diabetes mellitus 10
In the perioperative setting, acute use of GLP-1 RAs is associated with improved perioperative glycemic control, lower postoperative insulin requirements, lower risk of hypoglycemia, and improved cardiovascular outcomes 10