Glucagon-like peptide-1 (GLP-1) agonists are recognized for their efficacy in managing diabetes mellitus and aiding weight loss.1 They also reduce cardiovascular risk.2,3,4 The mechanism of action involves mimicking GLP-1, an incretin hormone that enhances insulin secretion after an oral glucose load.5,6 Beyond these effects, GLP-1 agonists are involved in inhibiting glucagon secretion, thus stabilizing blood glucose levels. They also play a role in maintaining islet cell mass and function, which is crucial in diabetes management.7 GLP-1 agonists influence multiple organs, notably the brain, pancreas, liver, kidneys, heart, and blood vessels, enhancing neuroprotective actions and mitigating systemic inflammation which may benefit recovery post-spinal surgery.2

Specifically, GLP-1 agonists protect and proliferate pancreatic islet B cells, promote nerve growth, reduce neuroinflammation, improve cardiac function, decrease appetite, slow gastric emptying, modulate lipid metabolism, and reduce fat deposition.6 Their impact on slowing gastric emptying is particularly relevant when considering the timing of medication cessation prior to surgery to minimize aspiration risk. While tachyphylaxis—the reduced efficacy of a drug after repeated administration—can occur with long-term use of these agonists, it may actually shorten the necessary fasting period before surgery due to a faster gastric emptying rate. This adjustment could lead to a decreased risk of aspiration and enhance surgical outcomes1. With the use of GLP-1 agonists broadening to include non-diabetic overweight patients seeking weight reduction—a group that now represents a large portion of our patient cohort—it's crucial to recognize the different clinical considerations this population presents. Consequently, the potential adverse effects must be carefully considered, especially when determining when to discontinue these medications in special situations, such as prior to procedures or surgeries requiring general anesthesia or monitored anesthesia care (MAC).

The current literature highlights potential adverse effects associated with the use of GLP-1 agonists during the pre-operative period. These medications have a longer half-life than endogenous GLP-1, which results in a prolonged effect on delaying gastric emptying and consequently may increase the risk of aspiration.8 A retrospective study has linked semaglutide use with elevated residual gastric content prior to elective esophagogastroduodenoscopy (EGD)9. In one case, a patient regurgitated a significant volume of gastric contents after the induction of anesthesia, despite having ceased taking the medication two days before surgery and fasting from solid foods for 20 hours beforehand.10 This led to the proposal that patients should suspend medication use four weeks prior to surgery.10 Another case involved a patient who, after fasting for 18 hours before the procedure and while on semaglutide, experienced intraoperative pulmonary aspiration.11 A further report detailed a case where an EGD, scheduled as part of bariatric surgery preparations, was canceled due to excessive gastric food retention.12 Collectively, these case reports underscore the potential risks involved with the use of GLP-1 agonists prior to surgical procedures. Prior to surgery, it is important to consider individualized measures to prevent intra-operative aspiration, tailored to each patient's circumstances. This includes evaluating the necessity and duration of withholding GLP-1 agonists and other medications known to affect gastric emptying. The British Journal of Anaesthesia identifies several risk factors for aspiration, including patient-related factors such as a full stomach, delayed gastric emptying, an incompetent lower esophageal sphincter, or esophageal disease; operative factors such as the type of surgery or patient positioning; anesthetic factors including light anesthesia, a difficult airway, positive pressure ventilation, and a longer duration of surgery; and device-related factors, such as the use of a laryngeal mask airway or any other supraglottic airway.13 Since delayed gastric emptying has been recognized as a risk factor for aspiration, a detailed medication history should be obtained to identify any potential contributors to this risk factor. Ultimately, the provider should advise the patient on the necessary steps to take prior to surgery to minimize the risk of intra-operative aspiration.

Clinicians must provide clear guidance to patients regarding medication use prior to procedures and surgeries. Unfortunately, due to gaps in current research, questions remain about how to optimally manage patients on GLP-1 agonists prior to surgery. The American Society of Anesthesiologists (ASA) Task Force on Preoperative Fasting recommends holding GLP-1 agonists on the day of the procedure for patients taking the medication daily.14 For weekly doses, the recommendation is to withhold the medication for one week prior to surgery. These guidelines apply to all patients using GLP-1 agonists, regardless of surgery type, medication indication, or dosage.14 If the patient exhibits GI symptoms on the day of the procedure, postponement should be considered due to the risk of regurgitation or aspiration.14 The Task Force further suggests adhering to the general ASA fasting guidelines, which recommend fasting from solid foods for six to eight hours or more, depending on the type of food.15,16 However, these guidelines are traditionally intended for healthy adults without conditions such as obesity and diabetes mellitus. This creates a challenge, as a recent study indicated that 70% of patients on semaglutide had residual gastric contents after fasting for at least 10 hours.17 Therefore, the optimal timing of fasting for diabetic patients and those on GLP-1 agonists may require further investigation, as the current general ASA recommendations may not be fully applicable to this patient population.