Glucagon-like peptide-1 (GLP-1) receptor agonists have quickly become an essential tool in managing type 2 diabetes. These drugs mimic the natural GLP-1 hormone by enhancing insulin secretion from the pancreas. In addition, their ability to improve glycemic control, promote weight loss, and provide cardiovascular benefits has increased their popularity among the general population. Available as daily and weekly formulations, these drugs present distinct pharmacological profiles that have implications for perioperative care, particularly concerning gastric emptying and glycemic management. Understanding the differences between weekly and daily GLP-1 agonists is critical for anesthesia providers to ensure safe and effective perioperative strategies.
Daily GLP-1 agonists, such as liraglutide, have a shorter half-life and require consistent daily dosing to maintain efficacy. These agents exhibit fluctuating plasma concentrations over a 24-hour cycle, which may result in a more predictable cessation of effects once discontinued.
In contrast, weekly formulations, such as semaglutide and dulaglutide, are designed for extended release. This feature provides more stable plasma levels over a week. Their prolonged activity contributes to their convenience and prolongs their pharmacological effect for several days after the last dose (1).
Despite these differences, both daily and weekly GLP-1 agonists share common side effects of nausea, vomiting, and slowed gastric motility, which have implications for anesthesia care. Delayed gastric emptying increases the risk of residual gastric contents at the time of anesthesia induction. This presents a heightened aspiration risk during general anesthesia, particularly if standard preoperative fasting guidelines are not followed (1).
These gastrointestinal effects may also cause exacerbation of postoperative nausea and vomiting (PONV), a risk increased in patients undergoing abdominal or laparoscopic surgeries. Weekly formulations may prolong these side effects postoperatively due to their extended action (1). These factors highlight the importance of tailored perioperative care for patients using GLP-1 agonists to ensure safety and reduce complications.
The primary method of mitigating these risks is the preoperative discontinuation of the medication. Some guidelines and research recommend discontinuing weekly GLP-1 agonists up to 7 days before surgery and daily formulations 24–48 hours prior to anesthesia and surgery (2). However, different institutions vary in their approaches to discontinuing these medications. In addition, discrepancies also exist between research findings and clinical practices, with some providers using uniform discontinuation timelines regardless of the specific agent (2, 3). This variability highlights the need for more clear, consistent, and evidence-based guidelines.
It is important to note that discontinuing these medications preoperatively, particularly for weekly formulations, may disrupt glycemic stability and increase the risk of hyperglycemia. To address this, preoperative assessments should include a thorough history of GLP-1 agonist use to guide anesthesia plans. These plans should incorporate proactive antiemetic measures, careful hydration management, and close monitoring of blood glucose levels during the perioperative period. Hyperglycemia increases the risk of infection, delayed wound healing, and other complications. Ultimately, alternative therapies, such as basal insulin, may be necessary to maintain stable blood glucose levels when GLP-1 agonists are withheld.
Further research is needed to optimize the perioperative treatment of patients on GLP-1 agonists. Studies exploring the optimal discontinuation timeline and strategies for minimizing postoperative complications will help bridge existing knowledge gaps.
References
1. Nauck MA, Meier JJ. Management of endocrine disease: GLP-1 receptor agonists and their role in postprandial glycaemic control. European Journal of Endocrinology. 2019;181(5):R211–R233. doi:10.1530/EJE-19-0337.
2. Thong KY, Jose B, Sukumar N. Peri-operative management of diabetes: Newer agents and devices. BJA Education. 2020;20(9):313–322. doi:10.1016/j.bjae.2020.05.006.
3. De Heide LJM, Teerenstra S, Lameijer H. Effects of GLP-1 analogues on perioperative outcomes: A systematic review. Diabetes, Obesity and Metabolism. 2022;24(2):301–311. doi:10.1111/dom.14553.