Why GLP-1 Receptor Agonists Matter in the OR: A Medical Student’s Guide

by William Haff & Collin Hunt

With each medication review, the names Semaglutide and Tirzepatide are becoming increasingly familiar — a reflection of their growing role in both diabetes management and the weight loss conversation. With this increase in usage, it is clear that understanding their impact on anesthetic delivery and management will be essential to maintaining a safe environment in the operating room. This enforces that medical students are able to translate and interpret these effects as they rotate through their anesthesiology clerkship and become practicing physicians. This article was prompted by an experience on an Interventional Cardiology rotation. The patient was being scheduled for a Watchman procedure and was recently started on Semaglutide for weight loss and was satisfied with her results. The patient questioned how starting this drug would affect her procedure and if she would need to be off of it for a certain period of time. By understanding their effects on anesthetic management, students will be able to answer this question confidently and continue to positively impact patient care.

Glucagon Like Peptide-1 is a hormone that is naturally produced in the human body, mostly by L cells located in the distal duodenum and ileum of the small intestine; but there is also a small amount produced in pancreatic alpha cells, as well as in the central nervous system. Its main effect is on the endocrine system, working to increase insulin secretion by increasing cAMP production in Beta islet cells in the pancreas causing a release of insulin, as well as blunting the response of glucagon producing alpha cells, further decreasing the glycemic burden. Although an important part of maintaining physiology is strictly monitoring a proper glucose range for each patient, the effects of GLP-1 agonists that future anesthesiologists should also be concerned with is the effect it has on gastric emptying and postoperative nausea and vomiting.

A long term side effect of diabetes is slowed gastric emptying due to hyperglycemia induced nerve damage from long term microangiopathy. Combine this with diabetic patients that are placed on GLP-1 agonists that further increase the risk of decreased gastric emptying, they are at an even higher risk of anesthetic complications such as aspiration and pneumonitis. Understanding this risk when proceeding with surgery is essential in maintaining a safe operation for all patients. Recent literature has emphasized that the risk of aspiration associated with GLP-1 receptor agonists is not only theoretical but clinically relevant, especially in procedures involving sedation or general anesthesia. A 2024 review in the journal Anaesthesia discussed the importance of individualized fasting protocols and suggested that a one-size-fits-all approach may not be appropriate for patients on these agents due to the variable effects on gastric motility.

The previous guidelines put forth by the American Society of Anesthesiologist for elective procedures was to hold daily dosed GLP-1 medications on either the day of surgery or the day prior. For GLP-1 medications that are dosed weekly, the guidelines stated holding medications one week prior to surgery. Along with these guidelines are the recommendations for patients that were not told/ did not comply with them; which may include use of ultrasound or other imaging modalities to determine the burden of stomach contents. An article that was more recently published in October 2024, suggests that having patients continue their GLP-1 agonist up until surgery and follow a liquid only diet 24 hours before surgery may be sufficient. The article states that patients that are at high risk of aspiration should have a point of care ultrasound to assess for food quantity in the stomach. This article emphasized that some patients are at a higher risk for aspiration than others, such as those with a recent increase in dosage of their GLP-1 medication, or those with current GI side effects from the medication, and that those people should be evaluated carefully and have elective procedures possibly delayed. In our experience in clinical practice, both guidelines are being used, with many patients stating that their surgeon asked them to stop taking the medication one week before. This highlights the need for more awareness of the updated ASA recommendations on GLP-1 agonist usage and surgery.

The article published by the American Journal of Gastroenterology looked at these recommendations and performed a retrospective analysis comparing endoscopically visualized retained gastric food during EGD completion during 2023 before and after the original ASA guidelines were published in August that year. They found that “before ASA guidelines were implemented, 50% of patients on a standard length fast while taking GLP-1 agonists for DM were found to have RGF during endoscopy. After ASA guidelines were introduced, zero patients with a prescribed GLP-1 agonist on an extended fast had RGF on endoscopy.” Their data supported the idea that prolonged fasting combined with the ASA guidelines for patients on GLP-1 agonists, significantly decreased the potential for aspiration in patients undergoing EGD.

Another well-known adverse effect of GLP-1 agonists is nausea and vomiting, a common complaint among patients on these medications. Interestingly, certain anesthetics—such as etomidate, along with common opioids like fentanyl and morphine—are also associated with these same side effects. This raises the question: Are patients on GLP-1 agonists at a higher risk for postoperative nausea and vomiting (PONV) compared to the general population? A study published in Surgery for Obesity and Related Diseases found that preoperative exposure to GLP-1 agonists was linked to an increased risk of PONV, particularly in patients undergoing laparoscopic sleeve gastrectomy. This risk was notably elevated at higher doses of GLP-1 agonists. To provide optimal care, it would be beneficial for healthcare providers to identify whether a patient is on a GLP-1 agonist, as this knowledge could inform anesthesia planning. This may involve using medications with a lower likelihood of causing PONV or implementing an effective antiemetic regimen to improve the patient's postoperative experience.

So what does this mean for us, the eager medical student looking to share the knowledge we conquered during our first two years of didactics? This means that whether you are on your surgery, emergency medicine, internal medicine, anesthesia or really any rotation, there will be a patient that is on a GLP-1 agonist that needs to undergo sedation and you will have knowledge of current guidelines, how to handle their care and understand the implications that these medications have on their perioperative management.

References

American Society of Anesthesiologists. (2024, October 29). Most patients can continue diabetes, weight loss GLP-1
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Multi-Society GLP-1 Clinical Practice Guidance Released.
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Gioe, Brennan MD1,*; Gioe, Scott MD2. S879 Are ASA Guidelines Regarding the Holding of GLP-1 Agonists
Before Endoscopy Enough to Reduce Aspiration Risk?. The American Journal of Gastroenterology 119(10S):p S610,
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Joshi, G., & Abdelmalak, B. (2023, June 29). American Society of Anesthesiologists Consensus-based guidance on
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Mizubuti, Gustavo B., Ho, Albert M.-H., Muniz da Silva, Lucas, Phelan, Robert. Perioperative management of
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