The debate over GLP-1 drugs and anesthesia safety
Less rigorous research methods contribute to confusion over the path forward.
Anesthesiologists are urging caution in interpreting a growing body of new research on the perioperative safety of GLP-1 medications during anesthesia. The emerging evidence has fueled debate over how seemingly contradictory findings should be interpreted and what they should mean for clinical practice.
Ion Hobai, MD, PhD, an Assistant Professor of Anesthesiology at Harvard Medical School in Boston, said design choices and other unmeasured factors on some studies have resulted in contradictions.
“Studies from anesthesiology and gastroenterology groups consistently demonstrate that, without additional precautions, patients on GLP-1s are more likely to present for elective procedures with unsuspected ‘full stomachs.’ This aligns with previous findings from gastroenterology groups confirming that these medications impede gastric emptying,” Dr. Hobai said. “However, large retrospective studies using nationwide patient databases show no increase (and sometimes even a decrease) in documented periprocedural pulmonary aspiration events.”
That discrepancy is the basis of the Sunday session, “Unraveling the GLP-1 Agonist Controversy: How a Critical Analysis of Study Design Can Reconcile Apparent Contradictions.”
The issue has attracted extraordinary attention from the anesthesiology community. According to Dr. Hobai, who will moderate the session, more studies have been published on GLP-1s and perioperative risk in just a few years than on several traditional aspiration risk factors that have been studied for decades. Researchers from both anesthesiology and gastroenterology have repeatedly found that patients taking GLP-1 drugs are more likely to present with unexpectedly full stomachs despite standard fasting protocols.
However, large database studies have produced seemingly contradictory findings. Dr. Hobai cautions against conflicting study results, saying they may be misleading and that many of these studies included patients who were already managed with enhanced anti-aspiration precautions, making it difficult to determine what would happen if such safeguards were not in place.
“Perhaps not surprisingly, the hurried accumulation of scientific data regarding GLP-1s has been associated with a decreased emphasis on scientific rigor. Motivated by the urgency of the problem, many studies have been published without adequately acknowledging the inherent limitations of their approach, which constrains the generalizability of their results,” Dr. Hobai said. “Often, researchers have minimized the significance of inclusion criteria and outcome definitions, leading to conclusions that are, at least at a superficial analysis, contradictory.”
According to session panelist Chelsea J. Messinger, MD, PhD, the strength of evidence showing increased residual gastric content (RGC) among GLP-1 users is concerning. A 2025 meta-analysis involving more than 165,000 patients found nearly a six-fold increase in residual gastric content, while several other studies reported significantly higher rates compared with non-users. Nevertheless, large cohort studies have consistently failed to identify a statistically significant increase in aspiration risk. Dr. Messinger is an Anesthesiology Resident at Massachusetts General Hospital, an Epidemiologist affiliated with the Harvard T.H. Chan School of Public Health, and an Editorial Fellow at the British Journal of Anaesthesia.
“There is consistent evidence that GLP-1s increase RGC in fasted patients, which is pharmacologically plausible given their known effects on gastric emptying,” Dr. Messinger said. “Yet, despite RGC being elevated in GLP-1 users who present for surgery, this has not translated into a detectable increase in aspiration in the observational literature. However, the degree to which these findings should inform practice is not straightforward.”
According to Dr. Messinger, the apparent discrepancy may partly reflect challenges in studying this question using observational data. She notes that certain design choices can introduce biases that complicate estimation of the causal relationship between exposures like GLP-1s and outcomes like aspiration. She emphasizes that careful study design is critical to obtaining valid estimates and interpreting findings, and that, when the goal is to inform clinical care, observational study design and analysis must align with the clinical question at hand.
The debate has influenced clinical guidelines around the world, she said. More than a dozen professional organizations across North America, Europe, Australia, and New Zealand have issued recommendations regarding perioperative management of GLP-1 drugs.
Recent guidance, she said, has shifted away from blanket recommendations to stop GLP-1 medications before surgery. Instead, experts increasingly emphasize 24-hour clear liquid diets for some or all patients and a risk-based approach that considers individual factors such as gastrointestinal symptoms, dose escalation, and preexisting gastric motility disorders.
Gastric ultrasound has emerged as a promising method to identify patients with significant gastric contents on the day of surgery, potentially reducing unnecessary cancellations. However, variation in recommendations, particularly surrounding preoperative fasting, reflects continued uncertainty about optimal perioperative management.
Despite the growing volume of research, both Drs. Hobai and Messinger agree that critical questions remain unanswered. Further research, including both observational and randomized studies, is needed to determine whether withholding GLP-1 medications, extending fasting times, or adopting specific perioperative management strategies improves patient outcomes.
“We are in the midst of a fluid and evolving scientific process. Times like these are best navigated with patience, realism, and what Bertrand Russell referred to as ‘intelligent doubt,’” Dr. Hobai said. “It is crucial to keep in mind that the most vocal and assured proponents often ignore the nuances, caveats, and potential sources of error inherent in a complex issue such as this. We currently lack a single, guaranteed solution, but we are significantly better informed than we were three years ago. If we continue this scientific momentum, I do believe that we will soon find an optimal approach to GLP-1s, and, in the process, elevate the standards of clinical research and evidence-based practice in anesthesia.”
The Sunday session will also feature panelist Adriana Oprea, MD, Associate Professor of Anesthesiology at Yale School of Medicine in New Haven, Connecticut.
