Submitted:
06 June 2025
Posted:
10 June 2025
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Abstract
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes mellitus (T2DM), obesity, and cardiovascular risk reduction. As these medications become more common, perioperative clinicians must understand their implications. Recent data suggest GLP-1 RAs may delay gastric emptying and increase the risk of aspiration during anesthesia. This narrative review summarizes current evidence, highlights clinical guidelines, and offers a perioperative management framework for patients on GLP-1 RAs, including semaglutide, liraglutide, dulaglutide, and others. We also present a clinical decision table to guide perioperative medication holds and patient risk stratification.
Keywords:
GLP-1 receptor agonists
; Perioperative management
; Aspiration risk
; Surgical complications
; Enhanced recovery after surgery (ERAS)
Introduction
GLP-1 receptor agonists are a cornerstone in modern management of metabolic diseases. Their popularity has surged due to benefits in weight reduction, glycemic control, and cardioprotection. However, perioperative challenges have emerged, particularly concerning delayed gastric emptying, a pharmacologic feature that may elevate aspiration risk during general anesthesia. Despite increasing clinical encounters with these agents, perioperative guidance remains inconsistent across institutions. This review outlines the clinical implications of GLP-1 RAs and provides actionable recommendations for perioperative providers.
Mechanism of Action of GLP-1 RAs
GLP-1 is an incretin hormone secreted by L cells in the small intestine in response to nutrient intake. GLP-1 RAs mimic this hormone by stimulating insulin secretion, suppressing glucagon release, and slowing gastric emptying via central and local gut mechanisms. These properties explain their efficacy in lowering blood glucose and promoting satiety but also underlie the potential anesthetic complications in surgical patients.
Preoperative Considerations
The primary concern is gastroparesis-like effects. In non-diabetic individuals and diabetics alike, GLP-1 RAs delay gastric emptying—this may persist even after drug discontinuation due to the long half-lives of weekly formulations like semaglutide (T½ ~7 days). Reported cases of intraoperative aspiration have led to heightened scrutiny.
- History Taking: Evaluate symptoms of nausea, vomiting, early satiety, bloating, and GERD.
- Medication Timing: Know last dose, formulation (daily vs. weekly), and renal function.
- ASA & Guidelines: ASA’s recent recommendations suggest holding GLP-1 RAs before elective surgery, though not all providers adhere consistently.
Intraoperative Risks and Recommendations
Aspiration risk is the central issue. Even with appropriate NPO status, delayed gastric clearance may leave residual stomach content. Anesthetic implications include:
- Increased aspiration pneumonia risk
- Delayed emergence or GI ileus postoperatively
- Unpredictable glucose dynamics
Anesthesia Implications:
- Consider rapid sequence induction (RSI)
- Use of gastric ultrasound in uncertain cases
- Delay surgery if recent GLP-1 dose taken and GI symptoms present
Postoperative Management
Postoperatively, the focus shifts to resumption of therapy and glycemic control:
- When to Restart: Resume GLP-1 RA when oral intake is tolerated without nausea/vomiting.
- Glycemic Monitoring: Risk of hyperglycemia if held >1 week; consider bridging strategies if needed.
- Nutrition: Reintroduce slowly with antiemetic support if needed.
Perioperative Management of GLP-1 Receptor Agonists
| Drug | Dosing | Half-Life | Hold Before Surgery | Restart After Surgery | Key Risks |
| Semaglutide (Ozempic, Wegovy) | Weekly | ~7 days | Hold 1 week prior | Resume when tolerating PO | Aspiration, delayed gastric emptying |
| Dulaglutide (Trulicity) | Weekly | ~5 days | Hold 1 week prior | Resume when tolerating PO | Aspiration |
| Liraglutide (Victoza, Saxenda) | Daily | ~13 hrs | Hold 1 day prior | Resume when tolerating PO | GI intolerance |
| Exenatide ER (Bydureon) | Weekly | ~2 weeks | Hold 2 weeks prior | Resume when tolerating PO | Prolonged effect |
| Exenatide IR (Byetta) | BID | ~2.4 hrs | Hold day prior | Resume when tolerating PO | Mild delay gastric emptying |
| Lixisenatide | Daily | ~3 hrs | Hold day prior | Resume when tolerating PO | Mild delay gastric emptying |
Clinical Decision Table
| Scenario | GLP-1 RA Use | Recommendation | Rationale |
| Weekly GLP-1 RA within 7 days of elective surgery | Yes | Consider holding 1 week prior | Delayed gastric emptying increases aspiration risk |
| Daily GLP-1 RA taken <24 hours prior | Yes | Hold morning of surgery | Residual gastric contents may persist |
| GI symptoms (nausea, vomiting, bloating) | Yes or No | Delay surgery or evaluate with gastric ultrasound | Active symptoms increase risk |
| No GI symptoms + held GLP-1 RA appropriately | No | Proceed with standard NPO guidelines | Lower aspiration risk |
| Emergent surgery | Yes or No | Use RSI or consider gastric suction/US | No time to safely withhold medication |
Conclusions
As GLP-1 RAs become integral in chronic disease management, anesthesiologists, surgeons, and internists must coordinate care to mitigate perioperative risks. Holding GLP-1 RAs prior to surgery, particularly weekly formulations, may reduce aspiration risk. Institutional protocols should reflect evolving guidelines. Until more data emerge, a cautious, individualized approach remains essential.
Author Contributions
I, Brendan Jones, conceptualized the review, conducted the literature search, synthesized the findings, and wrote the manuscript.
Funding
No external funding was received for this work.
Conflict of Interest
The author declares no conflicts of interest.
Use of AI Tools
This manuscript was prepared with the assistance of AI language models to enhance clarity, grammar, and structure. All intellectual content, critical analysis, and interpretation of data remain the sole responsibility of the author.
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