How long should tirzepatide (a glucagon-like peptide-1 (GLP-1) receptor agonist) be held before elective surgery?

Holding Tirzepatide Before Elective Surgery

Tirzepatide should be discontinued at least 7 days before elective surgery due to its effects on gastric emptying and increased risk of pulmonary aspiration. 1

Rationale for Discontinuation

Tirzepatide, as a dual GIP/GLP-1 receptor agonist, significantly affects gastric emptying which creates important perioperative considerations:

• Half-life of approximately 5 days 1
• Associated with delayed gastric emptying that can persist despite fasting
• Increased risk of pulmonary aspiration during anesthesia induction

Evidence Supporting Discontinuation

The 2025 multidisciplinary consensus statement from the Association of Anaesthetists and other societies provides the most current guidance on perioperative management of GLP-1 receptor agonists 1. This recommendation is based on:

• Multiple case reports of regurgitation and pulmonary aspiration in patients taking GLP-1 receptor agonists despite extended fasting periods 1
• Observational studies showing increased risk of retained gastric contents in patients on GLP-1 receptor agonists 1
• The European Medicines Agency's Pharmacovigilance Risk Assessment Committee highlighting the risk of delayed gastric emptying with these medications 1

Specific Recommendations for Tirzepatide

For tirzepatide specifically:

• Discontinue 7 days before elective surgery 1
• This timeframe accounts for tirzepatide's 5-day elimination half-life 1
• The extended washout period allows for reduction of drug effects on gastric motility

Important Clinical Considerations

1. Risk stratification:

   • Higher risk in patients with obesity
   • Higher risk with emergency procedures
   • Higher risk with procedures requiring general anesthesia

2. Anesthetic implications:

   • Consider rapid sequence induction when tirzepatide cannot be discontinued in time
   • Discuss with anesthesia team if surgery is urgent and discontinuation is not possible

3. Glycemic management:

   • Monitor blood glucose every 2-4 hours while NPO 1
   • Have short or rapid-acting insulin available for hyperglycemia 1
   • Resume tirzepatide postoperatively once oral intake is established

Common Pitfalls to Avoid

1. Inadequate discontinuation time: Standard fasting guidelines are insufficient for patients on tirzepatide - even patients who fasted for 18-20 hours have experienced aspiration 1

2. Failure to communicate medication use: Ensure the surgical and anesthesia teams are aware of tirzepatide use

3. Assuming tachyphylaxis eliminates risk: While long-term use may lead to some tachyphylaxis regarding gastric emptying effects, the risk of aspiration remains clinically significant 1

By following these recommendations, you can minimize the risk of perioperative complications while maintaining appropriate glycemic control in patients taking tirzepatide.