Glucagon-like Peptide-1 Agonists and the Anesthesiologist: Considerations and Management

Educational Objectives

The goal of this program is to improve outcomes in patients on glucagon-like peptide (GLP)-1 agonists undergoing surgery. After hearing and assimilating this program, the clinician will be better able to:

1. Determine the risk for residual gastric content in patients taking GLP-1 agonists.
2. Follow American Society of Anesthesiologists recommendations for discontinuing GLP-1 agonists in patients prior to elective surgery.

Summary

Glucagon-like peptide-1 (GLP-1) agonists: GLP-1 is a gut derived incretin hormone that stimulates insulin secretion from pancreatic β cells, reduces glucagon secretion from α cells, inhibits gastric emptying, reduces appetite, and suppresses gastric and duodenal peristalsis by vagal effects; its receptors are present throughout the body but are abundant in pancreas; the half-life of endogenous hormone is 1 to 2 min, but commercially available hormones have longer half-lives; it affects the pancreas, liver, kidneys, bone, stomach, heart, and brain; its effect on the brain increases satiety and reduces stroke risk; it also has cardioprotective effects; semaglutide (Ozempic, Rybelsus, Wegovy) was initially approved in 2017; these drugs are mostly injectable with one oral semaglutide formulation; these drugs reduce blood sugar, lower glycated hemoglobin (HbA_1C), and reduce insulin needs; they have low risk for hypoglycemia; related to cardioprotective effects, these drugs control blood pressure, decrease body mass index, improve cholesterol profile, improve glomerular filtration, and also have direct effects on cardiac myocytes resulting in better endothelial function and microvascular perfusion; a study reported 28% risk reduction in cardiac events; weight reduction is a key reason for increased use of GLP-1 agonists; the primary reasons for its weight loss effect was delayed gastric emptying and central appetite suppression; weight loss was related to increased satiety and reduced oral intake complemented by lifestyle modifications including other behavioral programs and surgery; tirzepatide (Mounjaro) has effects on GLP-1 and gastric inhibitory peptide

Side effects: are most commonly related to the gastrointestinal system (eg, nausea, vomiting, diarrhea); they also cause delayed gastric emptying; cholelithiasis and pancreatitis are other potential side effects; other less common side effects are hypersensitivity, acute kidney injury, and caution regarding medullary carcinoma of the thyroid

Considerations in scheduled elective surgery: assess the nothing-by-mouth status of the patient; some drugs are prescribed only for diabetes mellitus (DM) and some for DM and weight loss; these drugs have variations in their half-lives; semaglutide is available in injectable and oral formulations, and the half-life is 6 to 7 days; the dose is higher for obesity than for glycemic control; tachyphylaxis is an important consideration when assessing the duration of gastric emptying effect as gastric motility (vagal mediated) is subject to drug tolerance; a study reported reduced cause for concern after 8 to 12 wk; another paper reported sufficiency of standard fasting time after 12 wk; delay was most notable for the first postprandial hours and earlier treatment and becomes less significant later; scintigraphy is considered to be more standard than paracetamol absorption test for measuring gastric emptying; a study using scintigraphy reported sustained delay in gastric emptying after 12 wk, suggesting gastric emptying delay continues long into treatment; GLP-1 infusions in healthy volunteers may not necessarily extrapolate to patients on the commercial drug; the researchers found 56% of GLP-1 users has residual gastric content (RGC) compared with 19% in controls by ultrasonography; there was no significant association between increased RGC and short- or long-term duration of therapy

Aspiration risk: aspiration risk is multifactorial and depends on the patient, surgery, and time of last diet (full stomach, lower esophageal sphincter tone, esophageal disease, delayed gastric emptying from other causes); anesthesia characteristics to be considered are light anesthesia, supraglottic airways, positive pressure ventilation, and long surgery duration; Silveira et al (2023) reported a 5-fold increased risk for RGC with semaglutide taken before esophagogastroduodenoscopy; the study reported a 5% overall incidence of RGC in controls compared with 24% in the semaglutide group; combined upper and lower endoscopy had a low incidence of RGC, which is expected because of bowel preparation and low residue diet in preparation for colonoscopy; the effect of GLP-1 agonists is possibly dose dependent, thus having different effect on patients with DM and with obesity; Kobori et al (2023) reported 10 times increase in RGC in patients on semaglutide (5.4% vs. 0.5%); Stark et al (2022) reported 4-fold increase in RGC (6.8% vs. 1.7%); Sen et al (2024) showed a higher prevalence of RGC in users (19%) for elective procedures independent of DM diagnosis; the RCG was elevated beyond 7 days, decreasing each day; stopping the drug 1 wk before surgery may not be sufficient; Wu et al (2024) reported RGC in 19% in the GLP-1 agonist group compared with 5% in the control group

Gastric ultrasonography for measuring gastric content: is quick, easy, and noninvasive; it can be helpful for making decisions to cancel a case and can potentially modify the anesthetic strategy; 3% to 5% of imaging may be inconclusive

RGC and pulmonary aspiration: aspiration is rare in clinical practice; not every regurgitation results in aspiration; not every aspiration means prolonged mechanical ventilation; not every prolonged mechanical ventilation results in a fatality; in patients with DM and not on semaglutide, identifying a gastric volume considered significant (12%) but is not significantly different than nondiabetic patients; a study reported no higher risk for respiratory complications in patients on GLP-1 agonists undergoing emergency surgery; patients may not report semaglutide use as it may be considered an aesthetic treatment; a retrospective analysis of 62 nondiabetic patients taking semaglutide found that only 34% voluntarily disclosed the use of drug; as these medications are available online through telemedicine, these may not be recorded in the charts and electronic medical records

Challenges: diabetic patients have a higher risk for gastroparesis; patients taking these drugs for weight loss require higher doses; considerations include optimal timing for holding, duration of treatment (role of tachyphylaxis), and association between RGC and aspiration risk; gastric ultrasonography is helpful but has certain limitations

Strategies: some literature proposes that holding the drug for 1 half-life is insufficient; the question is whether it should be extended and if extended, does the patient requires bridge therapy; prolonged fasting itself is not beneficial; potential measures to mitigate the risk include rapid sequence intubation, prokinetic drugs (data unavailable for efficacy), changing the anesthesia plan (secured airways vs sedation), employing gastric ultrasonography, and gastric decompression before emergence

Risk mitigation: the American Society of Anesthesiologists advises to stop GLP-1 agonists 1 day (for daily dosing) and 1 wk (for weekly dosing) before surgery irrespective of its indication (DM or weight loss), dose, or type of surgery for elective cases; consult endocrinology if the drug is stopped beyond this duration; if gastrointestinal symptoms, such as nausea, vomiting, or abdominal pain or bloating, on the day of surgery, consider delaying an elective procedure and discuss the concern with the patient and surgeon; if the medication is not stopped for the duration as advised, consider full stomach precautions; consider evaluating gastric volume through ultrasonography and proceed if the stomach is empty; if the stomach is full, consider delaying the procedure or follow full stomach precautions; no evidence is available to suggest an optimal duration of fasting; delayed gastric emptying decreases with long-term use because of tachyphylaxis; there are concerns for pulmonary aspiration with general anesthesia or deep sedation exists, so consider regional anesthesia or moderate sedation; gastrointestinal symptoms may suggest RGC; one study suggests holding the drug for 3 half-lives to allow clearance of 88% of the drug, but this could lead to weight gain if treatment is for weight loss or affect glycemic control if treatment is for DM; consulting an endocrinologist in such cases is important; it is currently unclear if risk can be significantly reduced by holding the drug for multiple half-lives

Readings

Chen Y, Zink T, Chen Y, et al. Postoperative aspiration pneumonia among adults using GLP-1 receptor agonists. JAMA Netw Open. 2025;8(3):e250081. doi:10.1001/jamanetworkopen.2025.0081; Dixit AA, Bateman BT, Hawn MT, et al. Preoperative GLP-1 Receptor Agonist Use and Risk of Postoperative Respiratory Complications. JAMA. 2024;331(19):1672-1673. doi:10.1001/jama.2024.5003; Filippatos TD, Panagiotopoulou TV, Elisaf MS. Adverse effects of GLP-1 receptor agonists. Rev Diabet Stud. 2014;11(3-4):202-230. doi:10.1900/RDS.2014.11.202; Gulak MA, Murphy P. Regurgitation under anesthesia in a fasted patient prescribed semaglutide for weight loss: a case report. Régurgitation sous anesthésie chez une personne à jeun à qui du sémaglutide a été prescrit pour une perte de poids: une présentation de cas. Can J Anaesth. 2023;70(8):1397-1400. doi:10.1007/s12630-023-02521-3; Kobori T, Onishi Y, Yoshida Y, et al. Association of glucagon-like peptide-1 receptor agonist treatment with gastric residue in an esophagogastroduodenoscopy. J Diabetes Investig. 2023;14(6):767-773. doi:10.1111/jdi.14005; Mendes FF, Carvalho LIM, Lopes MB. Glucagon-like peptide-1 agonists in perioperative medicine: to suspend or not to suspend, that is the question. Braz J Anesthesiol. 2024;74(6):844538. doi:10.1016/j.bjane.2024.844538; Sen S, Potnuru PP, Hernandez N, et al. Glucagon-like peptide-1 receptor agonist use and residual gastric content before anesthesia. JAMA Surg. 2024;159(6):660-667. doi:10.1001/jamasurg.2024.0111; Sherwin M, Hamburger J, Katz D, et al. Influence of semaglutide use on the presence of residual gastric solids on gastric ultrasound: a prospective observational study in volunteers without obesity recently started on semaglutide. Influence de l’utilisation du sémaglutide sur la présence de solides gastriques résiduels à l’échographie gastrique: une étude observationnelle prospective auprès de volontaires sans obésité ayant récemment commencé à prendre du sémaglutide. Can J Anaesth. 2023;70(8):1300-1306. doi:10.1007/s12630-023-02549-5; Silveira SQ, da Silva LM, de Campos Vieira Abib A, et al. Relationship between perioperative semaglutide use and residual gastric content: a retrospective analysis of patients undergoing elective upper endoscopy. J Clin Anesth. 2023;87:111091. doi:10.1016/j.jclinane.2023.111091; Stark JE, Cole JL, Ghazarian RN, et al. Impact of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA) on Food Content During Esophagogastroduodenoscopy (EGD). Ann Pharmacother. 2022;56(8):922-926. doi:10.1177/10600280211055804; Umpierrez G, Pasquel FJ, Duggan E, et al. Should we stop glucagon-like peptide-1 receptor agonists before surgical or endoscopic procedures? Balancing limited evidence with clinical judgment. J Diabetes Sci Technol. Published online March 11, 2024. doi:10.1177/19322968241231565; Wu F, Smith MR, Mueller AL, et al. Association of glucagon-like peptide receptor 1 agonist therapy with the presence of gastric contents in fasting patients undergoing endoscopy under anesthesia care: a historical cohort study. Association d’un traitement par agonistes des récepteurs du peptide-1 de type glucagon avec la présence de contenu gastrique chez des personnes à jeun bénéficiant d’une endoscopie sous anesthésie: une étude de cohorte historique. Can J Anaesth. 2024;71(7):958-966. doi:10.1007/s12630-024-02719-z.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Wenzel was recorded at the 2024 Annual Convention and Conclave of the American Osteopathic College of Anesthesiologists, held September 7-10, 2024, in Palm Springs, CA, and presented by the American Osteopathic College of Anesthesiologists. For information on future CME activities from this presenter, please visit https://www.aocaonline.org/. Audio Digest thanks the speakers and the American Osteopathic College of Anesthesiologists for their cooperation in the production of this program.

CME/CE INFO

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Lecture ID:

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