What does a GLP‑1 receptor agonist (e.g., liraglutide, semaglutide, dulaglutide, exenatide) do, and why should it be discontinued before surgery?

What GLP-1 Receptor Agonists Do and Why We Continue Them Before Surgery

Based on the most recent 2025 multidisciplinary consensus statement, patients taking GLP-1 receptor agonists should continue these medications before surgery rather than discontinue them, with full risk assessment and implementation of aspiration mitigation strategies 1.

What GLP-1 Receptor Agonists Do

GLP-1 receptor agonists (liraglutide, semaglutide, dulaglutide, exenatide) work through several mechanisms 2, 3:

• Glucose-dependent insulin secretion: Stimulate insulin release only when blood glucose is elevated, minimizing hypoglycemia risk
• Glucagon suppression: Lower glucagon secretion in a glucose-dependent manner, reducing hepatic glucose output
• Delayed gastric emptying: Slow the rate at which food leaves the stomach, particularly in the early postprandial phase 3
• Increased satiety: Promote fullness and reduce appetite, leading to weight loss
• Cardiovascular and renal protection: Provide benefits beyond glycemic control in patients with diabetes

The Perioperative Controversy: A Paradigm Shift

The Old Approach (2024 and Earlier)

Earlier guidelines recommended holding GLP-1 receptor agonists for at least three half-lives before surgery (approximately 3 weeks for semaglutide) due to concerns about delayed gastric emptying and aspiration risk 4. This was based on case reports of regurgitation/aspiration and evidence of retained gastric contents 4.

The New Approach (2025 Consensus)

The 2025 multidisciplinary consensus from major UK and international societies fundamentally changed this recommendation 1. After a three-round modified Delphi process involving surgeons, anesthetists, physicians, pharmacists, and patients, the consensus now states:

Patients taking GLP-1 receptor agonists and dual GIP/GLP-1 agonists should:

• Continue these drugs before surgery
• Undergo full risk assessment and stratification
• Receive perioperative techniques that mitigate aspiration risk

This represents a major shift from routine discontinuation to routine continuation with risk mitigation.

Why the Change in Recommendations?

The 2025 consensus recognized several critical issues with routine discontinuation 1:

1. Glycemic control deterioration: Prolonged cessation (weeks) causes significant worsening of diabetes control in patients taking these medications for diabetes
2. Loss of cardiovascular protection: These medications reduce major adverse cardiac events perioperatively
3. Insufficient evidence: Discontinuation for 7 days did not decrease retained gastric contents, and there's no evidence that 3 half-lives ensures an empty stomach 4
4. Practical impossibility: Waiting 3-5 half-lives (up to 5 weeks for some agents) is clinically impractical for most surgical procedures

Risk Mitigation Strategy (The Current Standard)

Instead of discontinuation, implement these aspiration risk reduction measures 1, 4:

High-Risk Patients Requiring Enhanced Precautions:

• Recently started medication or dose escalation
• Symptoms of nausea, vomiting, or abdominal distention
• Unable to hold medication for any duration
• Taking other medications that delay gastric emptying (opioids, proton pump inhibitors, tricyclic antidepressants)

Specific Mitigation Strategies:

1. Preoperative assessment: Document medication dose, timing, symptoms, and other gastroparesis risk factors 4
2. Dietary modification: Consider clear liquid diet for period before standard fasting 4
3. Point-of-care gastric ultrasound: Use to assess residual gastric contents and guide decision-making 4
4. Prokinetic agents: Consider metoclopramide or erythromycin preoperatively 4
5. Airway management: Use rapid-sequence intubation when general anesthesia is required 4
6. Gastric decompression: Consider in very high-risk patients 4
7. Regional anesthesia: Prefer when feasible 5

Special Considerations by Indication

For Diabetes Management:

• Continue medication 1
• Benefits of glycemic control and cardiovascular protection outweigh aspiration concerns 4
• Consult endocrinology only if considering discontinuation for bridging therapy 4

For Weight Loss (Non-Diabetic):

• Still continue per 2025 consensus 1
• Earlier 2024 guidelines suggested holding for 3 half-lives in this population 4, but the most recent multidisciplinary consensus does not make this distinction
• Higher doses used for weight loss may prolong gastric stasis 4

Critical Pitfalls to Avoid

1. Don't automatically discontinue: The 2025 consensus explicitly recommends continuation, not cessation 1
2. Don't assume standard fasting is insufficient: Standard fasting times remain appropriate for most patients 4
3. Don't ignore FDA warnings but contextualize them: FDA labels warn about pulmonary aspiration risk 2, 3 but note that "available data are insufficient to inform recommendations" about discontinuation
4. Don't treat all patients the same: Risk-stratify and apply enhanced precautions selectively 1

Shared Decision-Making

Discuss with patients 4:

• The aspiration risk (rare but serious)
• Benefits of continuing medication (glycemic control, cardiovascular protection, weight maintenance)
• Mitigation strategies being employed
• Option to postpone elective surgery if concerns exist

The Bottom Line

The evidence-based approach has evolved from routine discontinuation to routine continuation with risk mitigation 1. The 2025 multidisciplinary consensus represents the highest quality, most recent guidance and should supersede earlier recommendations to hold these medications. This pragmatic approach balances the theoretical aspiration risk against the proven benefits of continuing therapy, while implementing specific strategies to minimize perioperative complications.