Semaglutide, more commonly known by the brand names Ozempic®, Rybelsus®, and Wegovy™ is a glucagon-like peptide-1 (GLP-1) agonist that has been used for several years in the management of type 2 diabetes mellitus (T2DM). Ozempic® and its cousins are recognizable names now because of their role in weight loss programs. The first GLP-1 agonist was approved for use in Canada in 2017.1 Figure 1 shows the numerous physiological effects of GLP-1 agonists, affecting a wide range of systems including the brain, muscle, pancreas, liver and heart.
Fig. 1
Of particular interest in this article is the function of GLP-1 as a hormone released by the gut during periods of eating that then stimulates the secretion of insulin. This lowers blood glucose levels by mobilising glucose molecules into the liver as well as adipose tissue and muscles.2 Other examples of GLP-1 agonists available in Canada include dulaglutide (Trulicity®), liraglutide (Saxenda®), lixisenatide (Adlyxine®), and tirzepatide (Mounjaro®). Semaglutide and the other GLP-1 agonists have the added benefit of central effects on the hunger centres in the hypothalamus as well as delaying gastric emptying to increase fullness and suppress appetite, a valuable tool for both the treatment of diabetes and weight loss management, but a potential risk for the use of sedation/anaesthesia. Table 1 compares some of the GLP-1 agonists available in Canada.
Table: Comparison chart for GLP-1 agonist drugs currently available in Canada.
| GLP-1 Agonist | Indication | Dose Frequency | Dose | Route of Administration |
| Ozempic® (semaglutide) | T2DM | Once Weekly | 0.25-1 mg | Subcutaneous Injection |
| Rybelsus® (semaglutide) | T2DM | Once Daily | 3-14 mg | Tablet |
| Wegovy™ (semaglutide) | Weight Loss | Once Weekly | 1.7-2.4 mg | Subcutaneous Injection |
| Trulicity® (dulaglutide) | T2DM | Once Weekly | 0.75-1.5 mg | Subcutaneous Injection |
| Saxenda® (liraglutide) | Weight Loss | Once Daily | 0.6-1.8 mg | Subcutaneous Injection |
| Adlyxine® (lixisenatide) | T2DM | Once Daily | 10-20 mcg | Subcutaneous Injection |
| Mounjaro® (tirzepatide) | T2DM | Once Weekly | 2.5-5 mg | Subcutaneous Injection |
Ozempic® was approved by the U.S. Food and Drug Administration (FDA) and by Health Canada in 2017 for glucose control but has found a significant increase in off-label use for weight management. Only Wegovy™ and Saxenda® have been approved for use as weight-loss medications by Health Canada.4 When used in conjunction with lifestyle modifications, significant reductions in weight occur within a one-year period. One study published in 2021 compared 1961 adults in a weight-loss program using either a once-weekly semaglutide subcutaneous injection with lifestyle changes or placebo with lifestyle changes for 68 weeks. Those taking semaglutide had a 14.9% decrease in body weight compared to 2.4% the placebo group. Due to these significant and reproducible results and because of the economic impact of the North American weight loss industry ($USD145.57 billion per year [$CAD197.9 billion]), semaglutide received nine million prescriptions in the United States within the last quarter of 2022, resulting in medication shortages expected to last well into 2024.5,6,7
The FDA recommends semaglutide for weight loss if patients meet one of the following criteria:
- Body Mass Index (BMI) ≥ 27 kg/m2 (overweight) and have a weight-related comorbidity (e.g., high blood pressure, type 2 diabetes, hypercholesterolemia).
- BMI ≥ 30 kg/m2 (obese class I).
- Approved doses of oral semaglutide range from 3 mg to 14 mg and subcutaneous semaglutide doses range from 0.25 mg to 2.4 mg, with higher doses being used for weight loss rather than glycemic control.
In a report published in November, 2023, based on data collected between 2015 and 2022, an estimated 30% of Canadian adults were classified as obese based on BMI measures (i.e., BMI greater than 30). That translated to an estimated 8.7 million obese adults in Canada in 2022.8 In the 2015 Canada Community Health survey, 60% of adult Canadians had a BMI greater than 25 kg/m2, with 43% of those being greater than 30 kg/m2. Continued surges in GLP-1 agonist prescriptions are expected, so clinicians that provide sedation/anaesthesia services must understand and account for the unique anaesthetic risks for these patients.
Anaesthetic Consideration
The American Society of Anesthesiologists (ASA) provides practice guidelines regarding preoperative fasting prior to anaesthesia. These guidelines advise patients to refrain from consuming solid foods at least eight hours and clear liquids for two hours prior to scheduled procedures requiring anaesthesia. This fasting period is meant to minimise the risk of aspiration of gastric contents, a potentially serious complication where gastric contents can enter the lungs during the procedure. This could lead to pulmonary aspiration, respiratory infections, and other life-threatening complications.
Concerns have recently been raised regarding whether patients taking GLP-1 agonists experience a degree of delayed gastric emptying that extends beyond that of the current fasting guidelines (i.e., eight hours for solid food). In a 2023 case report, a 31-year-old appropriately fasted female on Ozempic® was found to have significant amounts of solid food in her stomach during endoscopy.9 Other similar case reports prompted a retrospective analysis of endoscopy data and found a 5-fold increase in risk for residual gastric volume in those who take semaglutide even after appropriate fasting times. There was also an association with pre-operative gastrointestinal symptoms (e.g., nausea, vomiting, abdominal pain, bloating) and the degree of residual gastric contents.9,10 Risks of regurgitation and subsequent pulmonary aspiration during sedation, deep sedation, or general anaesthesia must be considered in these patients with delayed gastric emptying.
Best Practices to Reduce Risk of Aspiration During Sedation/Anaesthesia
To decrease gastric volume prior to sedation, thereby reducing the risk of aspiration, patients taking GLP-1 agonists either require doses of their medication to be held or to fast for longer periods than the current nil per os (NPO) guidelines. Currently, the effective length of time required for either of these management strategies is unknown.
Unfortunately, semaglutide has a metabolic half-life of seven days.11 It is often administered as a weekly subcutaneous injection, but it can also be taken daily orally, as previously noted in Table 1. Prolonged abstinence periods of two or even three weeks from this medication would likely be required to decrease the effects of delayed gastric emptying. Currently, there is no available evidence discussing the physical and mental implications of altering the drug regimens for these periods.
In cases where the medication cannot be withheld, patients can either have a gastric ultrasound to evaluate residual gastric volume, or they can be assumed to have a “full stomach”. The ultrasound option is unlikely to be available in ambulatory dental settings.
Both the Canadian Anesthesiologists’ Society (CAS) and the ASA have published statements regarding patient and medication management for those on GLP-1 agonists. Although these two groups operate in the context of medicine, there is considerable overlap with sedation/anaesthesia for dentistry. Their recommendations and resultant decision trees are summarized in Table 2 and Figure 2.
Table 2: Summary of anaesthetic-related recommendations and considerations for case management to reduce risks of aspiration.
| Recommendation/Consideration | Source |
| An extended NPO period. | CAS, ASA |
| A clear fluid diet for some period of time prior to the NPO period. | CAS |
| Rapid-sequence induction if [intubated] general anaesthesia is required. | CAS, ASA |
| Withhold the dose previous to the procedure (i.e., one day or one week). (Consult the patient’s endocrinologist if GLP-1 therapy is for management of diabetes.) | ASA, CAS |
| Consider delaying elective procedures if GI symptoms are present the day of the procedure. | ASA |
Fig. 2
Conclusion
The use of sedation and anaesthesia in dentistry boasts an exemplary safety record, contributing to its widespread acceptance and utilisation in the ambulatory and hospital settings. A new challenge has been presented with the steep rise in the use of GLP-1 agonists and their potential to induce delayed gastric emptying, which is associated with a high risk of potentially catastrophic complications including pulmonary aspiration, aspiration pneumonitis, and pneumonia.
The authors have presented current strategies based on available literature adapted from the CAS and the ASA. For dental patients undergoing deep sedation or general anaesthesia, best practices include holding daily GLP-1 agonists on the day of procedure and weekly GLP-1 agonists a week prior to procedure, and adhering to or extending the current ASA fasting guidelines, with the possibility of an addition period of a clear fluid diet ahead of the recommended fasting period. Future studies will examine the optimal fasting duration for patients on GLP-1 agonists to establish consensus guidelines.
For patients undergoing elective dental procedures under sedation, the practitioner must obtain a detailed medical history and updated medication list prior with special consideration for those who take GLP-1 agonists. Since their use is becoming more common, it is prudent to specifically inquire about the use of GLP-1 agonists when conducting a pre-operative assessment. As some patients may perceive their medications as only those in pill form or to deal with an illness, they may fail to include their regular use of GLP-1 agonists as part of their history. Careful consideration of all forms of medication should be made by dentists during the pre-operative assessment to ensure the safe administration of sedation. 
Oral Health welcomes this original article.
References
- Novo Nordisk Inc. Health Canada approves Victoza® as the first and only GLP-1 receptor agonist to reduce the risk of cardiovascular death in patients with type 2 diabetes and established cardiovascular disease. News release. November 21, 2017. https://www.newswire.ca/news-releases/health-canada-approves-victoza-as-the-first-and-only-glp-1-receptor-agonist-to-reduce-the-risk-of-cardiovascular-death-in-patients-with-type-2-diabetes-and-established-cardiovascular-disease-659046393.html. Accessed December 9, 2023.
- Saraiva, F. K., & Sposito, A. C. (2014). Cardiovascular effects of glucagon-like peptide 1 (GLP-1) receptor agonists. Cardiovascular Diabetology, 13(1).
- Trujillo, J.M., Nuffer, W., and Smith, B.A. (2021) GLP-1 receptor agonists: an updated review of head-to-head clinical studies. Therapeutic Advances in Endocrinology and Metabolism, 12: January-December. https://doi.org/10.1177/2042018821997320.
- Novo Nordisk Inc. Health Canada approves Wegovy™ for the treatment of adults with obesity. News release. November 25, 2021. https://www.newswire.ca/news-releases/health-canada-approves-wegovy-tm-for-the-treatment-of-adults-with-obesity-829324682.html. Accessed December 9, 2023.
- Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T. D., Wadden, T. A., Wharton, S., Yokote, K., Zeuthen, N., Kushner, R. F., & STEP 1 Study Group (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. The New England Journal of Medicine, 384(11), 989–1002. https://doi.org/10.1056/NEJMoa2032183
- Health Canada. (2023) The supply and use of Ozempic. https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-shortages/information-consumers/supply-notices/ozempic.html. October 30, 2023. Accessed December 9, 2023.
- Market Research Community. Weight Management Market Size, Share & Trends Analysis, By Type (Equipment, Services), By Equipment (Fitness Equipment, Surgical Equipment), By Application (Weight Maintenance, Body Shaping), By End Use, By Region and Forecast Period 2023 – 2030. https://marketresearchcommunity.com/weight-management-market/. Accessed December 9, 2023.
- Elflein, J. (2023) Percentage of Canadian adults that are overweight or obese based on BMI from 2015 to 2022. Statista, State of Health. https://www.statista.com/statistics/748339/share-of-canadians-overweight-or-obese-based-on-bmi/#statisticContainer. Accessed December 30, 2023.
- Fujino, E., Cobb, K. W., Schoenherr, J., Gouker, L., & Lund, E. (2023). Anesthesia Considerations for a Patient on Semaglutide and Delayed Gastric Emptying. Cureus, 15(7), e42153. https://doi.org/10.7759/cureus.42153. Accessed November 30, 2023.
- Silveira, S. Q., da Silva, L. M., de Campos Vieira Abib, A., de Moura, D. T. H., de Moura, E. G. H., Santos, L. B., Ho, A. M., Nersessian, R. S. F., Lima, F. L. M., Silva, M. V., & Mizubuti, G. B. (2023). Relationship between perioperative semaglutide use and residual gastric content: A retrospective analysis of patients undergoing elective upper endoscopy. Journal of clinical anesthesia, 87, 111091. https://doi.org/10.1016/j.jclinane.2023.111091. Accessed November 30, 2023.
- Hall, S., Isaacs, D., and Clements, J.N. (2018) Pharmacokinetics and Clinical Implications of Semaglutide: A New Glucagon-Like Peptide (GLP)-1 Receptor Agonist. Clinical Pharmacokinetics, 57: 1529-1538.
- https://www.cas.ca/CASAssets/Documents/Advocacy/Semaglutide-bulletin_final.pdf. Accessed November 30, 2023.
- https://www.asahq.org/about-asa/newsroom/news-releases/2023/06/american-society-of-anesthesiologists-consensus-based-guidance-on-preoperative. Accessed November 30, 2023.
About the Authors:
Dr. Lucia Santos is a current third-year dental anesthesiology resident at the University of Toronto, where she had previously completed her DDS degree. She can be reached at lucia.santos@mail.utoronto.ca.
Dr. Bruce Pynn is Oral Health’s editorial board member for oral and maxillofacial surgery. He is an Assistant Professor, North Ontario School of Medicine, Lakehead University, and Chief of Dentistry, Thunder Bay Regional Health Sciences Center.
Dr. Peter Nkansah is a Dental-Anesthesiologist with a private practice in Toronto. He is an editorial board member for Oral Health, an Assistant Professor at the University of Toronto’s Faculty of Dentistry and past president of the Canadian Academy of Dental Anesthesia.
