When should Mounjaro (tirzepatide) be stopped prior to surgery?

When to Stop Mounjaro (Tirzepatide) Prior to Surgery

Mounjaro (tirzepatide) should be discontinued at least 3 weeks before elective surgery to minimize the risk of pulmonary aspiration due to its prolonged gastric emptying effects. 1

Pharmacokinetic Considerations

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist with a long half-life of approximately 7 days 1. This extended half-life necessitates earlier discontinuation compared to other antidiabetic medications:

• The 3-week discontinuation period allows for approximately 88% of the drug to be cleared from the system 1
• This recommendation exceeds the American Society of Anesthesiologists' general guidance for weekly GLP-1 receptor agonists, which may be inadequate for tirzepatide specifically 1

Risk Assessment

The primary concern with perioperative tirzepatide use is delayed gastric emptying, which significantly increases the risk of pulmonary aspiration during anesthesia induction 1. Studies have shown:

• GLP-1 receptor agonists are associated with a substantially increased risk of pulmonary aspiration (OR 10.23,95% CI 2.94-35.82) 1
• The European Medicines Agency's Pharmacovigilance Risk Assessment Committee has specifically highlighted this concern 1

Perioperative Management Algorithm

Pre-Surgery Planning:

1. For elective procedures:

   • Discontinue tirzepatide at least 3 weeks before surgery 1
   • Monitor glycemic control and implement alternative diabetes management as needed

2. For urgent/emergency procedures (when 3-week discontinuation isn't possible):

   • Consider point-of-care gastric ultrasound to assess residual gastric contents 1
   • Implement rapid sequence intubation to reduce aspiration risk 1
   • Consider prokinetic medications (e.g., metoclopramide) preoperatively 1
   • In high-risk patients, consider gastric decompression 1

Risk Factors Requiring Special Attention:

• Recent initiation or dose increase of tirzepatide 1
• Presence of gastrointestinal symptoms (nausea, vomiting, abdominal distention) 1
• Co-prescribed medications that further delay gastric emptying (opioids, proton pump inhibitors, tricyclic antidepressants) 1

Glycemic Management During the Perioperative Period

While tirzepatide is discontinued, alternative glycemic control measures should be implemented:

• For patients with type 2 diabetes, consider temporary insulin therapy if needed 2
• Target perioperative blood glucose levels of 80-180 mg/dL (4.4-10.0 mmol/L) 3
• Monitor blood glucose every 2-4 hours while the patient is NPO 3
• Consider intravenous insulin for patients with poor glycemic control 3

Resumption After Surgery

Resume tirzepatide only when:

• The patient is eating normally
• No signs of acute illness or metabolic derangement are present
• The patient has fully recovered from anesthesia 1

Comparison with Other Medications

Unlike some medications that can be continued or stopped closer to surgery, tirzepatide requires a longer discontinuation period:

• Metformin: Withhold only on the day of surgery 3
• SGLT2 inhibitors: Discontinue 3-4 days before surgery 3
• Oral glucose-lowering agents: Withhold on the morning of surgery 3
• Antiplatelet agents: Variable timing (1-7 days depending on agent) 3

Pitfalls and Caveats

• Inadequate discontinuation time increases aspiration risk during anesthesia induction
• Balancing glycemic control against aspiration risk requires careful consideration
• The limited scientific evidence specifically for tirzepatide in the perioperative setting means recommendations are based on pharmacokinetic principles and experience with similar medications 4
• Consultation with the treating endocrinologist regarding optimal timing is advisable, especially for patients with poorly controlled diabetes 1