GLP-1 Agents Not Linked to Post-Op Aspiration Pneumonia, More Data Suggest

Preoperative use of GLP-1 receptor agonists was not significantly associated with short-term postoperative aspiration pneumonia, according to a retrospective cohort study.

Among over 366,000 patients who underwent one of 14 common surgical procedures, those using GLP-1 drugs had no difference in the odds of postoperative aspiration pneumonia within 30 days compared with non-users in an adjusted analysis (OR 0.78, 95% CI 0.57-1.06, P=0.12), reported Eric L. Smith, MD, of New England Baptist Hospital in Boston, and colleagues.

There was also no significant difference in the odds of acute respiratory failure (OR 0.98, 95% CI 0.89-1.06, P=0.57), they noted in JAMA Network Open.

“Given the lack of association found between GLP-1 receptor agonist use and short-term postoperative complications, reconsidering the preoperative GLP-1 receptor agonist withholding guidelines might be beneficial,” Smith’s group wrote.

Aspiration concerns with GLP-1 agents first emerged in June 2023 when the American Society of Anesthesiologists (ASA) advised users to stop taking them prior to elective surgery due to a potentially increased risk for regurgitation and pulmonary aspiration of gastric contents while under general anesthesia. This guidance was met with some pushback from the medical community.

By October 2024, ASA reversed its stance. In new guidance, it said most patients can continue their GLP-1 receptor agonist up until the day of surgery, but should follow a liquid diet for 24 hours before the procedure, depending on the specific circumstances.

Just a week later, the FDA added a warning to the labels of all GLP-1 drugs about pulmonary aspiration during general anesthesia or deep sedation. However, the labels don’t list any pulmonary aspiration risk mitigation recommendations, such as a temporary hold prior to surgery or modified preoperative fasting.

“With the escalating use and broadened indications of GLP-1 receptor agonists, healthcare practitioners are likely to encounter an increasing number of patients using these medications,” Smith and team wrote. “Since there are still insufficient data to support the long-term use of GLP-1 receptor agonists, clinicians should approach treatment of patients using GLP-1 receptor agonists with caution.”

For this study, Smith and co-authors used data from the MarketScan commercial claims database, which includes over 273 million U.S. patients annually, during the period prior to ASA’s 2023 recommendations. They included 366,476 patients who underwent one of 14 common, high-volume surgeries from April 2020 through September 2022, including groin hernia repair, hysterectomy, knee arthroplasty, hip arthroplasty, appendectomy, laminectomy, bariatric surgery, spinal fusion, tibial and ankle shaft fractures, colectomy, lower extremity amputation, thyroidectomy, hip fracture, and coronary artery bypass graft.

Median patient age was 53, 56.4% were women, and 1.6% had a preoperative prescription for a GLP-1 agent.

The researchers adjusted for sex, age, geographic region, comorbidities, and surgical acuity in their analysis.

GLP-1 agent users versus non-users were more likely to be female (59% vs 56.4%) and live in the South (51.9% vs 45.1%). They were also more likely to have obesity and diabetes (47.5% vs 6.8%), hypertension (69.6% vs 40.7%), and chronic kidney disease (6.4% vs 2.9%).

The most commonly used GLP-1 receptor agonist was semaglutide (Ozempic, Wegovy, Rybelsus; 42.9%), followed by dulaglutide (Trulicity; 38.7%), liraglutide (Victoza, Saxenda; 15.9%), and exenatide (Byetta, Bydureon BCise; 2.7%). Tirzepatide was not used in the trial.

Odds of aspiration pneumonia didn’t significantly differ between GLP-1 agent users and non-users across five sensitivity analyses adjusted for surgery type and anesthesia type, when including only patients with indications for GLP-1 agents, when excluding patients who died during index admission, and in a model using propensity score analysis.

Due to their use of a claims database, a prescription for a GLP-1 agent was used as a surrogate for use, and data on medication adherence were not available, the authors noted. Other limitations included the lack of information on preoperative factors, such as fasting duration, gastric ultrasonography findings, or cases canceled due to aspiration concerns, which may have underestimated aspiration events.

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