Does a Glucagon-like peptide-1 (GLP-1) agonist need to be stopped before surgery?

GLP-1 Agonists and Perioperative Management

GLP-1 receptor agonists should be held for at least three half-lives before surgery to reduce the risk of pulmonary aspiration, with different recommendations based on whether they're used for diabetes or weight loss. 1

What are GLP-1 Agonists?

GLP-1 receptor agonists are medications that:

• Mimic the action of the incretin hormone glucagon-like peptide-1
• Stimulate insulin secretion in a glucose-dependent manner
• Suppress glucagon secretion
• Delay gastric emptying
• Reduce appetite and food intake

Common GLP-1 agonists include:

• Short-acting: exenatide (Byetta)
• Long-acting: semaglutide (Ozempic, Wegovy), dulaglutide (Trulicity), liraglutide (Victoza, Saxenda)

Perioperative Recommendations for GLP-1 Agonists

For Weight Loss Patients

• Hold GLP-1 receptor agonist for at least three half-lives before surgery 1
• This allows approximately 88% of the drug to be cleared from the system
• For long-acting agents like semaglutide, this means stopping 3 weeks before surgery

For Type 2 Diabetes Patients

• Consult with the treating endocrinologist regarding: 1
  1. Risks and benefits of holding the drug for at least three half-lives
  2. Recommendations for bridging diabetic therapy if the GLP-1 agonist will be held longer than the next scheduled dosing time

Risk Assessment Factors

Identify high-risk patients who may need additional precautions: 1

• Those unable to hold GLP-1 agonist for three half-lives before procedure
• Recently started medication or increased dose
• Experiencing nausea, vomiting, or abdominal distention
• Taking other medications that delay gastric emptying (opioids, PPIs, TCAs)
• Recent intake of substances that delay gastric emptying (alcohol, cannabis)
• Previous gastro-esophageal surgery

Rationale for Recommendations

The primary concern with GLP-1 agonists perioperatively is delayed gastric emptying, which increases the risk of:

• Retained gastric contents
• Regurgitation during anesthesia induction
• Pulmonary aspiration

This risk is demonstrated in case reports of regurgitation under anesthesia in fasted patients taking semaglutide 2, even with prolonged fasting periods (20 hours for solids, 8 hours for clear fluids).

Risk Mitigation Strategies

If the GLP-1 agonist cannot be held for the recommended period or the patient is high-risk: 1

1. Consider postponement of elective procedures
2. Implement clear fluid diet before pre-operative fasting
3. Use prokinetic drugs (metoclopramide or erythromycin) pre-operatively
4. Perform point-of-care gastric ultrasound to assess residual gastric contents
5. Consider rapid-sequence intubation to reduce aspiration risk
6. Pre-emptive gastric decompression in very high-risk patients

Algorithm for Decision-Making

1. Determine indication for GLP-1 agonist:

   • Weight loss → Hold for three half-lives
   • Diabetes → Consult endocrinology

2. Assess if drug can be held for recommended time:

   • If yes → Hold and proceed with standard protocols
   • If no → Implement risk mitigation strategies

3. On day of procedure: 1

   • If GLP-1 agonist was withheld for three half-lives → Proceed
   • If not withheld for three half-lives:
     • Consider prokinetic drug
     • Perform gastric ultrasonography
     • If gastric volume >1.5 ml/kg → Consider delay
     • If proceeding → Use rapid sequence intubation

Special Considerations

The 2024 American Diabetes Association Standards of Care notes: "There are little data on the safe use and/or influence of GLP-1 receptor agonists on glycemia and delayed gastric emptying in the perioperative period." 1

While some evidence suggests GLP-1 agonists may improve glycemic control perioperatively 3, the risk of aspiration currently outweighs this potential benefit for most patients.

Balancing Risks and Benefits

The decision to discontinue GLP-1 agonists must balance:

• Risk of pulmonary aspiration (potentially life-threatening)
• Impact on glycemic control (especially for diabetes patients)
• Surgical urgency (elective vs. emergency)

For patients with diabetes, the disruption in glycemic control from stopping GLP-1 agonists may necessitate alternative glycemic management strategies during the perioperative period.