In a recent large population-based study published in the peer-reviewed Gastroenterology journal, researchers found that glucagon-like peptide-1 receptor agonist (GLP-1RA) medications—such as Ozempic and Wegovy that are integrally transforming medications in the management of type 2 diabetes and obesity—are associated with a higher risk of post-endoscopy aspiration pneumonia.
Aspiration pneumonia is caused by inhaling food or liquid, including gastric content, into the lungs, leading to inflammation (swelling) and infection of the lungs or large airways.
Endoscopy is a common diagnostic and therapeutic medical procedure to look inside the human body using a tube-like scope through a natural opening such as your mouth. Post-endoscopy aspiration pneumonia is a consequence of inadvertent inhalation of gastric contents into the lungs following endoscopy.
The current clinical practice is moving toward a goal of zero-harm endoscopy; however, delayed gastric emptying, called gastroparesis, and increased colonic transit time are common side effects of these medications that raise concerns about the possibility of aspiration pneumonia following endoscopy.
Gastric emptying is particularly problematic during endoscopy because it increases the risk of aspiration by producing retained gastric contents, which interfere with visualization during esophagogastroduodenoscopy (EGD). These gastric contents can be easily refluxed and aspirated (enter the lungs) due to the non-existent gag reflex as a result of the patient being under sedation.
In 2005, the U.S. Food and Drug Administration (FDA) approved the first GLP-1 agonist (exenatide). Since then, it has been dramatically used, especially following its approval for weight loss and its demonstrated efficacy in reducing cardiovascular risks and kidney protective mechanisms in diabetic patients. In fact, data from research studies showed that patients may lose up to 20% of their weight using these medications.
However, GLP-1RA medications have well-known stomach side effects—including nausea, vomiting, diarrhea, and constipation—as it works by slowing digestion. Moreover, due to its potent effect on gastrointestinal function, it can lead to delayed gastric emptying and alter intestinal motility. In simpler words, the patient's stomach may not empty completely during the standard fasting duration before endoscopy to avoid the risk of aspiration.
Case in point, a recent study confirms this trend as the proportion of residual gastric content, found during endoscopy, was 11 times higher among patients who use GLP-1RA (5.4% vs. 0.49%; P = 0.004).
Responding to the growing worries, in June 2023, a consensus-based guideline by The American Society of Anesthesiologists (ASA) considered holding GLP-1RAs prior to an endoscopic or surgical procedure to decrease the risk of aspiration pneumonia. Consequently, in November 2023, the American Gastroenterological Association (AGA) published a rapid clinical practice update discussing the lack of sufficient evidence supporting the medications held before endoscopic procedures and recommending an individualized approach for these patients.
Both societies acknowledged the increasing risk of aspiration and the lack of enough data to provide sufficient recommendations. This was endorsed by the multi-society statement—including AGA, AASLD, ACG, ASGE and NASPGHAN—entitled, “No data to support stopping GLP-1 agonists prior to elective endoscopy.”
The senior author, Ali Rezaie, MD—medical director of the GI Motility Program at Cedars-Sinai Medical Center in Los Angeles, California—sought to verify through empirical data whether these medications did, in fact, raise the risk of aspiration pneumonia.
This retrospective cohort study included almost 1 million de-identified U.S. patients ages 21 and 70—obtained from the TriNetX dataset, which includes 114 million de-identified health records from 80 healthcare organizations—who underwent upper and lower endoscopies between January 1, 2018, and December 21, 2020. Patients on a GLP-1 receptor agonist were identified as users of this medication for more than 6 months and 2 refills within 6 months before the procedure. To ensure the quality of the result, the researchers considered 59 factors—including obesity, medications, chronic diseases—that could affect the aspiration risks and alter the findings. After considering all of these factors, Rezaie and his colleagues found that patients using GLP-1RA medications had a statistically significant 33% higher chance of experiencing aspiration pneumonia than non-users (0.83% vs 0.63%) with a hazard ratio (HR) of 1.33. (95% CI 1.02-1.74).
This higher risk was also observed with other medications—including propofol—where Rezaie and his colleagues found a higher risk of aspiration pneumonia among patients with propofol sedation during endoscopies (HR, 1.49), likely due to diminished airway protective reflexes.
Beyond GLP-1RA medications, other factors were found to be associated with a high risk of aspiration pneumonia following endoscopy. In a meta-analysis study of 48,674 patients, researchers found that the average risk of post-endoscopy aspiration pneumonia was 1.9% with various risk factors identified, including old age ≥ 65 years, coexisting pulmonary disease, coexisting cerebrovascular disease, remnant stomach, sedation with propofol, and long procedural duration.