A newly published clinical investigation in the British Journal of Anaesthesia (May 2025 issue) reveals compelling evidence linking glucagon-like peptide-1 receptor agonists (GLP-1RAs) to impaired gastric emptying (IGE). These findings highlight potential risks for patients undergoing surgery, especially concerning pulmonary aspiration during anesthesia.

As GLP-1RAs continue to grow in popularity for managing type 2 diabetes and obesity, this pharmacovigilance study calls for increased awareness and careful perioperative planning among clinicians.

Understanding GLP-1 receptor agonists

What are GLP-1RAs?

GLP-1 receptor agonists are a class of injectable and oral medications that mimic the natural incretin hormone, GLP-1. They enhance insulin secretion, suppress glucagon release, slow gastric emptying, and promote satiety. These actions improve glycemic control and support weight loss.

Commonly prescribed GLP-1RAs:

• Exenatide (Byetta, Bydureon)
• Liraglutide (Victoza, Saxenda)
• Dulaglutide (Trulicity)
• Semaglutide (Ozempic, Wegovy, Rybelsus)
• Tirzepatide (Mounjaro)

Study overview: What was investigated?

Researchers analyzed data from the U.S. FDA Adverse Event Reporting System (FAERS), spanning from Q1 2004 to Q1 2024. The objective was to determine the association between GLP-1RA use and impaired gastric emptying (IGE), particularly in the context of anesthesia and surgical safety.

Key methods:

• Extraction of IGE reports labeled under the term “impaired gastric emptying” in MedDRA.
  
• Identification of the top 10 drugs linked to IGE.
  
• Disproportionality analysis using reporting odds ratios (ROR).
  
• Logistic regression to evaluate the influence of age, sex, and weight.
  
• Kaplan-Meier and Weibull analysis to determine time-to-onset trends.

Study results: what did they find?

1. GLP-1RAs dominate IGE-related reports

Among the top 10 drugs associated with IGE events, five were GLP-1 receptor agonists:

• Dulaglutide: 262 cases
  
• Semaglutide: 246 cases
  
• Exenatide: 183 cases
  
• Tirzepatide: 181 cases
  
• Liraglutide: 110 cases
  

Together, they accounted for 49.5% (982 of 1982) of the IGE reports among these top 10 drugs. Despite being only a subset of all drugs in the FAERS, this disproportionately high representation is significant.

2. Disproportionality signals for IGE

All five GLP-1RAs had statistically significant reporting odds ratios (RORs) for IGE:

• Semaglutide: ROR 24.8
  
• Dulaglutide: ROR 14.7
  
• Liraglutide: ROR 13.7
  
• Exenatide: ROR 5.4
  
• Tirzepatide: ROR 18.3
  

This analysis confirms that these drugs are significantly more likely to be reported in conjunction with IGE compared to other medications.

Time-to-onset and early treatment risk

Median onset of IGE after therapy initiation:

• Semaglutide: 40.5 days
  
• Liraglutide: 42 days
  
• Dulaglutide: 44 days
  
• Exenatide: 60 days
  
• Tirzepatide: 107.5 days
  

Early failure pattern

Weibull shape parameter (b) was < 1 for all five drugs, indicating that IGE risk is highest early in treatment, then tapers off over time. This “early failure” curve is consistent with tachyphylaxis, a reduced drug response after prolonged exposure.

Who is at higher risk?

Age, weight, and sex impact

• Older patients had a lower IGE risk with dulaglutide and semaglutide.
  
• Higher body weight and male sex were associated with lower IGE risk for exenatide.
  
• No significant sex- or weight-based risks were noted for liraglutide or tirzepatide.

This suggests that young, female, lower-weight patients may be more susceptible to IGE from GLP-1RA therapy.

Pulmonary aspiration risk: rare but severe

Of the 982 GLP-1RA-linked IGE cases, 13 (1.3%) led to pulmonary aspiration. These events included:

• 1 reported death
  
• 4 hospitalizations
  
• 2 life-threatening conditions
  
• 3 were classified as serious medical events
  

Even though aspiration was relatively rare, its severity emphasizes the importance of risk assessment before surgery.

Clinical implications for perioperative care

Why does IGE matter in surgery?

Delayed gastric emptying increases the risk of regurgitation and aspiration pneumonia during induction of anesthesia, an especially concerning event in unconscious patients.

Should GLP-1RAs be paused preoperatively?

Some institutions now recommend withholding GLP-1RAs for 1–2 weeks before elective procedures, particularly if the patient is early in treatment or shows symptoms of gastroparesis. However, standard guidelines are not yet unified.

Summary: key takeaways

• GLP-1 receptor agonists are strongly associated with impaired gastric emptying.
  
• The risk is highest early in therapy, with significant implications for surgical safety.
  
• Age, weight, and sex are meaningful modifiers of IGE risk.
  
• Pulmonary aspiration, though rare, can be life-threatening.
  
• Personalized perioperative planning is essential for patients on GLP-1RAs.
  

Reference: Huang H et al. Glucagon-like peptide-1 receptor agonists and impaired gastric emptying: a pharmacovigilance analysis of the US Food and Drug Administration adverse event reporting system. Br J Anaesth. 2025;134:1486-1496. 

For more information on GLP1R agonists and their impact on perioperative care, check out Anesthesia Updates on the NYSORA Anesthesia Assistant App. 

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