Perioperative GLP-1 Receptor Agonists

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for the treatment of type 2 diabetes and/or obesity. The physiological actions of endogenous GLP-1, and synthetic GLP-1RAs include inhibition of gastric emptying. This has peri-procedural implications due to the potential increased risk of retained gastric contents which may result in pulmonary aspiration. There is a need for local evidence-based guidelines to best manage patients on GLP-1RAs and dual GLP-1 and glucose-dependent insulinotropic polypeptide receptor co-agonists (GLP-1/GIPRAs) presenting for surgical and medical procedures requiring sedation or anaesthesia. A panel of experts was formed to consider the peri-procedural implications of GLP-1RA and GLP-1/GIPRA use and establish best practice recommendations based on the current evidence.We recommend that all patients should be asked about glucagon-like peptide-1 receptor agonist (GLP-1RA) and dual GLP-1 and glucose-dependent insulinotropic polypeptide receptor co-agonist (GLP-1/GIPRA) use prior to anaesthesia or sedation for surgical and endoscopic procedures and be informed of the benefits and risks. We also recommend that GLP-1RAs and GLP-1/GIPRAs be continued in the peri-procedural period. Preprocedural diet modification with a 24-h clear fluid diet, followed by standard 6-h fasting, should be recommended for all patients receiving GLP-1RAs or GLP-1/GIPRAs. In patients who have not completed or are unable to have a 24-h liquid diet, risk stratification using gastric ultrasound or minimally sedated gastroscopy to assess gastric contents is recommended, as is the use of intravenous erythromycin. We cannot currently recommend using the absence of gastrointestinal symptoms for risk stratification, nor can we recommend an adequate cessation period for GLP-1RAs and GLP-1/GIPRAs to ensure gastric emptying has returned to baseline levels. This clinical guideline, developed by multiple professional bodies, outlines current best practice recommendations for patients taking GLP-1RAs and combined GLP-1/GIPRAs who require general anaesthesia, sedation and/or endoscopic procedures. The guide provides a structure for Australian and New Zealand primary health practitioners, gastroenterologists, surgeons, endocrinologists, anaesthetists and perioperative physicians to support clinical decisions in these patients.

Glucagon-like peptide-1 receptor agonists are known to delay gastric emptying; however, the association between glucagon-like peptide-1 receptor agonist use and peri-operative pulmonary aspiration risk is not known. This systematic review and meta-analysis aimed to summarise the evidence on whether glucagon-like peptide-1 receptor agonist exposure is associated with pulmonary aspiration or increased residual gastric content in fasted patients undergoing procedures requiring anaesthesia or sedation. We searched six databases for studies assessing peri-operative pulmonary aspiration or residual gastric contents in fasted patients or volunteers who were using any form of glucagon-like peptide-1 receptor agonist. Pooled odds ratios were estimated for each outcome using random effects meta-analysis. Certainty of evidence for each outcome was assessed using the GRADE framework. Of 9010 screened studies, 28 observational studies were included. In a meta-analysis of nine studies involving 185,414 patients and 471 cases of pulmonary aspiration, glucagon-like peptide-1 receptor agonist exposure was not associated with pulmonary aspiration (OR 1.04, 95%CI 0.87-1.25, low certainty of evidence). In a meta-analysis of 18 studies involving 165,522 patients and 3831 cases of residual gastric contents, glucagon-like peptide-1 receptor agonist exposure was associated with an increased risk of residual gastric contents despite appropriate fasting (odds ratio 5.96, 95%CI 3.96-8.98, low certainty of evidence). In a meta-analysis of five studies involving 1706 patients and 208 cases of residual gastric contents, withholding at least one dose of glucagon-like peptide-1 receptor agonist before a procedure was associated with lower odds of residual gastric contents (odds ratio 0.51, 95%CI 0.33-0.81, very low certainty of evidence). Patients using glucagon-like peptide-1 receptor agonists are at increased risk of presenting for anaesthesia with residual gastric contents, though the available evidence does not indicate that this translates to an increased risk of pulmonary aspiration.

Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist used for management of type 2 diabetes and/or obesity. To test the hypothesis that perioperative semaglutide use is associated with delayed gastric emptying and increased residual gastric content (RGC) despite adequate preoperative fasting, we compared the RGC of patients who had and had not taken semaglutide prior to elective esophagogastroduodenoscopy. The primary outcome was the presence of increased RGC. Single-center retrospective electronic chart review. Tertiary hospital. Patients undergoing esophagogastroduodenoscopy under deep sedation/general anesthesia between July/2021-March/2022. Patients were divided into two (SG&#xa0;=&#xa0;semaglutide, NSG&#xa0;=&#xa0;non-semaglutide) groups, according to whether they had received semaglutide within 30&#xa0;days prior to the esophagogastroduodenoscopy. Increased RGC was defined as any amount of solid content, or&#xa0;>&#xa0;0.8&#xa0;mL/Kg (measured from the aspiration/suction canister) of fluid content. Of the 886 esophagogastroduodenoscopies performed, 404 (33 in the SG and 371 in the NSG) were included in the final analysis. Increased RGC was observed in 27 (6.7%) patients, being 8 (24.2%) in the SG and 19 (5.1%) in the NSG (p&#xa0;<&#xa0;0.001). Semaglutide use [5.15 (95%CI 1.92-12.92)] and the presence of preoperative digestive symptoms (nausea/vomiting, dyspepsia, abdominal distension) [3.56 (95%CI 2.2-5.78)] were associated with increased RGC in the propensity weighted analysis. Conversely, a protective [0.25 (95%CI 0.16-0.39)] effect against increased RGC was observed in patients undergoing esophagogastroduodenoscopy combined with colonoscopy. In the SG, the mean time of preoperative semaglutide interruption in patients with and without increased RGC was 10.5&#xa0;&#xb1;&#xa0;5.5 and 10.2&#xa0;&#xb1;&#xa0;5.6&#xa0;days, respectively (p&#xa0;=&#xa0;0.54). There was no relationship between semaglutide use and the amount/volume of RGC found on esophagogastroduodenoscopy (p&#xa0;=&#xa0;0.99). Only one case (in the SG) of pulmonary aspiration was reported. Semaglutide was associated with increased RGC in patients undergoing elective esophagogastroduodenoscopy. Digestive symptoms prior to esophagogastroduodenoscopy were also predictive of increased RGC.

Prescriptions and use of glucagon-like peptide-1 (GLP-1) receptor agonists are increasing dramatically, as indications are expanding from the treatment of diabetes mellitus to weight loss for people with obesity. As GLP-1 receptor agonists delay gastric emptying, perioperative healthcare practitioners could be concerned about an increased risk for pulmonary aspiration during general anaesthesia. We summarise relevant medical literature and provide evidence-based recommendations for perioperative care for people taking GLP-1 receptor agonists. GLP-1 receptor agonists delay gastric emptying; however, ongoing treatment attenuates this effect. The risk of aspiration during general anaesthesia is unknown. However, we advise caution in patients who recently commenced on GLP-1 receptor agonists. After over 12 weeks of treatment, standard fasting times likely suffice to manage the risk of pulmonary aspiration for most otherwise low-risk patients.

The purpose of this American Gastroenterological Association (AGA) Institute Rapid Clinical Practice Update (CPU) Communication is to review the available evidence and provide expert advice regarding the evolving management of patients taking GLP-1 receptor agonists prior to endoscopy. This CPU was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. This communication incorporates important and recently published studies in this field, and it reflects the experiences of the authors who are experts in bariatric medicine and/or endoscopy.

To quantify the extent of metabolic and cardiovascular rebound following the discontinuation of GLP-1 receptor agonist (GLP-1RA) therapy in adults with obesity, type 2 diabetes, or type 1 diabetes, and identify potential modifiers of these outcomes. We conducted a systematic review and meta-analysis of randomized controlled trials including adults and adolescents treated with GLP-1RAs, followed by a post-discontinuation follow-up of at least 12 weeks. Databases searched included MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and ClinicalTrials.gov, with no language restrictions, and published up to October 17, 2025. We assessed changes in anthropometric, glycemic, cardiovascular, and lipid parameters between the end of treatment and the post-cessation period. Random-effects models were used to calculate pooled mean differences. The risk of bias and certainty of evidence were evaluated using the Cochrane ROB 2.0 and GRADE frameworks. The study was registered with PROSPERO under CRD42025646185. Eighteen RCTs (3771 participants) were included. Among individuals with obesity, discontinuation of GLP-1RA resulted in significant metabolic rebound, characterized by a body weight gain of 5.63 kg (95% CI: 3.52-7.73, I2 = 99.57%, moderate) and an increase in HbA1c of 0.25% (95% CI: 0.18-0.32, I2 = 98.45%, moderate). Waist circumference, BMI (Body Mass Index), SBP (Systolic Blood Pressure), and FPG (fasting plasma glucose) also showed significant deterioration. In the type 2 diabetes setting, weight gain was 2.03 kg (95% CI: 1.63-2.42, I2 = 42.28%, moderate), and HbA1c rose by 0.65% (95% CI: 0.22-1.08, I2 = 96.83%, moderate), while FPG remained stable (0.90 mmol/L; 95% CI: -0.36 to 2.17, I2 = 98.81%, moderate). Subgroup analyses revealed greater weight regain with longer follow-up (>26 weeks: 7.31 kg vs. 2.51 kg) and with semaglutide compared to liraglutide (8.21 kg vs. 4.29 kg). Semaglutide also led to greater increases in waist circumference (3.80 cm vs. 2.69 cm) and SBP (7.09 mmHg vs. 1.56 mmHg). Most outcomes showed no evidence of significant publication bias, with minor asymmetry detected for VLDL (very-low-density lipoprotein) levels in individuals with obesity and for weight change (kg) in patients with type 2 diabetes. The risk of bias assessment using the ROB 2.0 tool rated all included studies as having a low risk. The magnitude and consistency of these effects underscore the physiological consequences of GLP-1RA discontinuation. As the clinical use of GLP-1RAs continues to grow in the management of obesity and diabetes, it is imperative that treatment guidelines address not only initiation and titration but also discontinuation and long-term maintenance strategies to sustain therapeutic gains. This study received no funding.