Should I hold Zepbound (tirzepatide) before elective surgery, and how long prior to the procedure?

Should Zepbound (Tirzepatide) Be Held Before Elective Surgery?

Yes, Zepbound should be held before elective surgery due to the risk of delayed gastric emptying and pulmonary aspiration, with the specific duration depending on the type of procedure and anesthetic technique.

Recommended Holding Period

For elective procedures, hold Zepbound for at least 1 week (7 days) before surgery. 1 This recommendation is based on tirzepatide's elimination half-life of approximately 5 days, and stopping one week prior allows for adequate drug clearance to minimize aspiration risk. 1

Key Pharmacokinetic Rationale

• Tirzepatide has an elimination half-life of 5 days 1
• Weekly dosing means the drug accumulates and requires extended washout periods
• Gastric emptying delays persist throughout treatment, though the effect of tachyphylaxis remains unclear 1

Risk Assessment Framework

High-Risk Scenarios Requiring Strict Adherence

Procedures requiring general anesthesia or airway manipulation carry the highest aspiration risk and mandate the full 1-week holding period. 1 Case reports document pulmonary aspiration despite prolonged fasting (up to 20 hours) in patients on GLP-1/GIP agonists, including tirzepatide. 1

• Multiple case reports show regurgitation and aspiration occurring even with extended fasting periods (10-20 hours for solids) 1
• One tirzepatide case involved regurgitation with undigested food and gastric secretions despite appropriate fasting 1
• The odds ratio for pulmonary aspiration with GLP-1 receptor agonists in elective surgery is 10.23 (95% CI 2.94-35.82) 1

Procedure-Specific Considerations

Upper endoscopy and procedures involving supraglottic airways carry particularly high risk. 1 Studies in endoscopy settings show a hazard ratio of 1.33 (95% CI 1.02-1.74) for aspiration-related complications. 1

Critical Implementation Details

Timing of Last Dose

• The last dose should be administered no later than 7 days before the scheduled procedure 1
• For a Monday surgery, the last dose should be the previous Monday or earlier
• Do not attempt to "taper" the dose—simply discontinue 1

Fasting Does Not Eliminate Risk

Standard preoperative fasting guidelines are insufficient in patients recently on tirzepatide. 1 Even 18-20 hour fasting periods have not prevented aspiration in documented cases. 1 The drug's effect on gastric emptying persists beyond what fasting can compensate for.

Balancing Competing Risks

Risks of Holding Tirzepatide

The 2025 multidisciplinary consensus acknowledges that drug cessation has adverse impacts that must be considered: 1

• Loss of glycemic control in patients with diabetes
• Potential weight regain
• Loss of cardiovascular benefits

However, the risk of pulmonary aspiration with its potential for mortality outweighs these concerns for elective procedures. 1

When Shorter Holding Periods Might Be Considered

The evidence suggests less certainty about aspiration risk in patients on long-term GLP-1/GIP therapy due to possible tachyphylaxis effects on gastric emptying. 1 However, given the catastrophic nature of pulmonary aspiration and documented cases despite long-term use, the conservative 1-week holding period should still be applied. 1

Anesthetic Technique Modifications

If surgery cannot be delayed and tirzepatide was taken within the past week:

• Consider rapid sequence intubation with cricoid pressure 1
• Have suction immediately available 1
• Consider point-of-care gastric ultrasound to assess gastric contents 1
• Strongly consider postponing truly elective procedures 1

Common Pitfalls to Avoid

1. Do not rely on patient-reported fasting duration alone—the drug effect persists regardless 1
2. Do not assume tachyphylaxis has eliminated the risk in long-term users—case reports include patients on therapy for months 1
3. Do not confuse tirzepatide with daily GLP-1 agonists—the 5-day half-life requires longer holding periods than daily formulations 1
4. Do not restart immediately postoperatively—wait until normal bowel function returns and oral intake is established 1

Postoperative Resumption

Resume tirzepatide only after:

• Adequate hemostasis is confirmed
• Normal bowel function has returned
• Patient is tolerating oral intake
• Typically 24-48 hours minimum for minor procedures, 2-3 days for major surgery 1

Urgent/Emergency Surgery Exception

For truly urgent or emergency surgery where delaying 7 days is not possible, proceed with enhanced aspiration precautions including rapid sequence intubation, but recognize the significantly elevated risk. 1 The decision must weigh the urgency of the surgical indication against aspiration risk on a case-by-case basis.