Summary Safety Review - Glucagon-like Peptide 1 Receptor Agonists (GLP-1 RAs) (dulaglutide, liraglutide, lixisenatide, semaglutide and tirzepatide) - Assessing the Potential Increased Risk of Pulmonary Aspiration in Patients Undergoing Procedures Requiring General Anesthesia or Deep Sedation

Review decision

A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.


Product
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) (dulaglutide-, liraglutide-, lixisenatide-, semaglutide- and tirzepatide-containing products)
Potential Safety Issue
Pulmonary aspiration (unintentional inhalation of stomach contents, such as food or liquid, into the trachea or lungs) in patients undergoing procedures requiring general anesthesia or deep sedation
Key Messages

  • Health Canada’s review found a possible link between the use of GLP-1 RAs and the increased risk of pulmonary aspiration in patients undergoing procedures requiring general anesthesia or deep sedation.

  • The product safety information in the Canadian product monograph (CPM) for all GLP-1 RAs has been updated to include the increased risk of pulmonary aspiration in patients undergoing procedures requiring general anesthesia or deep sedation.

Overview

It is known that GLP-1 RAs delay gastric emptying (slow the rate at which the stomach releases food into the small intestine). Retained gastric contents are a risk factor for pulmonary aspiration in the context of general anesthesia or deep sedation. Although there is often overlap, pulmonary consequences of aspiration can be divided into 3 clinical syndromes: mechanical obstruction (physical blockage), chemical pneumonitis (inflammation of the lower lungs directly caused by the inhaled substance), and bacterial aspiration pneumonia (bacterial infection caused by inhaling a substance with a high level of bacteria).

Health Canada reviewed the potential increased risk of pulmonary aspiration in patients taking GLP-1 RAs and undergoing procedures requiring general anesthesia or deep sedation. The safety review was triggered by the publication of communications by the Canadian Anesthesiologists’ Society and the American Society of Anesthesiologists aimed at raising awareness of the increased risk of pulmonary aspiration during surgical procedures in patients taking GLP-1 RAs. To ensure safe anesthesia and sedation, these communications highlighted the importance of recognizing that, despite complying with preoperative fasting guidelines (instructions for patients to not consume any food or liquids for a specific duration before surgery), patients treated with GLP-1 RAs are at an increased risk of retained gastric (stomach) content.

Use in Canada

  • Glucagon-like peptide 1 receptor agonists are a class of prescription drugs authorized for sale in Canada:

    • for the medical management of adults with type 2 diabetes (Ozempic/Rybelsus [semaglutide], Plosbrio [semaglutide], Victoza [liraglutide], Trulicity [dulaglutide], Xultophy [insulin degludec and liraglutide], Mounjaro [tirzepatide] and Soliqua [insulin glargine and lixisenatide])

    • for chronic weight management in adults and adolescents with obesity or who are overweight (Wegovy [semaglutide], Poviztra [semaglutide], Saxenda [liraglutide] and Zepbound [tirzepatide])

    • to treat metabolic dysfunction-associated steatohepatitis (MASH) (a severe form of metabolic-associated fatty liver disease that develops when fat buildup in the liver causes inflammation and scarring) in adults with moderate to advanced liver scarring (fibrosis), but not with cirrhosis (a type of liver disease) (Wegovy)a

    • to prevent the worsening of kidney disease and death from cardiovascular (having to do with the heart and blood vessels) disease in adults who have both chronic kidney disease and type 2 diabetes (Ozempic)

    • to reduce the risk of certain serious cardiovascular events in adults with type 2 diabetes and established cardiovascular disease and/or chronic kidney disease as an add-on to other standard treatments (Ozempic)

    • to reduce the risk of non-fatal heart attacks in adults with established heart disease and a body mass index (BMI) equal to or greater than 27 kg/m2 (Wegovy and Poviztra)

    • to reduce the risk of death from cardiovascular disease in adults with type 2 diabetes and established cardiovascular disease (Rybelsus and Victoza as an add-on to other standard treatments)

    • to reduce the risk of non-fatal stroke in adults with type 2 diabetes and risk factors for heart disease, or established cardiovascular disease (Trulicity)

  • Glucagon-like peptide 1 receptor agonists have been marketed in Canada since 2010. All GLP-1 RA products are available as subcutaneous (under the skin) injections. Semaglutide is also available as an oral tablet.

  • Approximately 8.8 million prescriptions for GLP-1 RAs were dispensed by Canadian retail pharmacies in 2024.

Safety Review Findings

  • Health Canada reviewed the available information from searches of the Canada Vigilance databaseb and the scientific literature.

  • Health Canada reviewed 21 cases (1 Canadian and 20 international) of pulmonary aspiration in patients undergoing general anesthesia or deep sedation, including 5 unique cases from the published literature.1-5 Of the 21 cases, 3 (international) were found to be probably linked to the use of GLP-1 RAs, 3 (1 Canadian and 2 international) were possibly linked and 1 (international) was unlikely to be linked. The remaining 14 cases were unassessable due to missing clinical information.

  • Health Canada also reviewed real-world data from published sources6-7, which support a link between GLP-1 RAs and retained gastric contents, a known risk factor for pulmonary aspiration during general anesthesia or deep sedation, and an increased number of procedures that could not be completed.

Conclusions and Actions

  • Health Canada’s review found a possible link between the use of GLP-1 RAs and the increased risk of pulmonary aspiration in patients undergoing general anesthesia or deep sedation.

  • The product safety information in the CPM for all GLP-1 RAs has been updated to include this increased risk of pulmonary aspiration in patients undergoing procedures requiring general anesthesia or deep sedation.

  • Since the completion of Health Canada’s review, other products in the GLP-1 RA drug class (Plosbrio and Poviztra) were authorized. Health Canada is working with the manufacturers of these products to update their respective CPMs.

  • Healthcare professionals are encouraged to consider the increased risk of residual gastric content due to delayed gastric emptying, along with possible mitigation strategies, prior to performing surgeries or procedures with general anesthesia or deep sedation.

  • Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of GLP-1 RAs, and other health products, to the Canada Vigilance Program.

  • Health Canada will continue to monitor safety information involving GLP-1 RAs, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified.

Additional Information

The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of GLP-1 RAs both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

References

  1. Anazco D, et al. Low incidence of pulmonary aspiration during upper endoscopy in patients prescribed a glucagon-like peptide‑1 receptor agonist. Clin Gastroenterol Hepatol. 2024;22(6):1333‑1335. doi.org/10.1016/j.cgh.2023.11.024

  2. Avraham SA, et al. Pulmonary aspiration of gastric contents in two patients taking semaglutide for weight loss. Anaesth Rep. 2024;12(1):e12278. doi:10.1002/anr3.12278

  3. Dong T, et al. Pulmonary aspiration during upper endoscopy in a patient prescribed semaglutide. Rev Esp Enferm Dig. 2024. doi:10.17235/reed.2024.10844/2024

  4. Santos LB, Nersessian RSF, Silveira SQ, et al. A call to update anesthetic protocols: the hidden risks of semaglutide. Can J Anesth. 2024;71:1175‑1176. doi:10.1007/s12630‑024‑02774‑6

  5. Weber M, Siddarthan I, Mack PF. Clinically significant emesis in a patient taking a long-acting GLP‑1 receptor agonist for weight loss. Br J Anaesth. 2023;131(2):e37‑e39. doi:10.1016/j.bja.2023.05.005

  6. Singh S, et al. Effects of glucagon-like peptide‑1 receptor agonists on endoscopy outcomes: systematic review and meta-analysis. Gastrointest Endosc. 2025;101(2):343‑349. doi.org/10.1016/j.gie.2024.10.011

  7. Facciorusso A, et al. Effects of glucagon-like peptide‑1 receptor agonists on upper gastrointestinal endoscopy: a meta-analysis. Clin Gastroenterol Hepatol. 2025;23(5):715‑725. doi.org/10.1016/j.cgh.2024.07.021

Footnotes

  1. Wegovy was approved with conditions (NOC/c) for this indication, which means it has passed Health Canada’s review and can be marketed in Canada under the condition that the manufacturer completes additional studies to confirm the clinical benefit of the product for this indication. 

  2. Canadian reports can be accessed through the Canada Vigilance Online Database.

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