Is it more important to hold semaglutide (GLP-1 receptor agonist) 1 week before surgery or empagliflozin (SGLT2 inhibitor) 3 days before surgery?

Holding Semaglutide vs. Empagliflozin Before Surgery: Which Is More Important?

It is more important to hold semaglutide (GLP-1 receptor agonist) for at least three half-lives (approximately 3 weeks) before surgery than empagliflozin (SGLT2 inhibitor) for 3 days, due to the significantly higher risk of pulmonary aspiration with semaglutide despite prolonged fasting. 1

Rationale for Prioritizing Semaglutide Discontinuation

GLP-1 Receptor Agonists (Semaglutide)

• Mechanism of concern: Significantly delays gastric emptying, leading to retained gastric contents despite prolonged fasting
• Evidence of risk: Multiple case reports document regurgitation and pulmonary aspiration in patients taking semaglutide despite extended fasting periods (16-20 hours) 1, 2
• Discontinuation timing: Should be held for at least three half-lives (approximately 3 weeks for semaglutide) to clear 88% of the drug 1
• Persistent risk: Studies show that discontinuing semaglutide for only 7-10 days did not decrease the prevalence of retained gastric contents 1, 3

SGLT2 Inhibitors (Empagliflozin)

• Mechanism of concern: Risk of euglycemic diabetic ketoacidosis
• Recommended discontinuation: 3-4 days before surgery per FDA guidelines 4
• Risk mitigation: More straightforward monitoring and management compared to aspiration risk

Risk Assessment Algorithm

1. For patients on both medications:

   • Hold semaglutide for 3 weeks before surgery
   • Hold empagliflozin for 3-4 days before surgery

2. If surgery is urgent and cannot be delayed:

   • Consider semaglutide the higher risk medication
   • Implement full aspiration precautions:
     • Rapid sequence induction
     • Pre-operative gastric ultrasound
     • Consider prokinetic drugs (metoclopramide)
     • Consider pre-emptive gastric decompression in high-risk cases

Special Considerations

Indication-Specific Approach for Semaglutide

• Weight loss indication: Higher risk - discontinue for at least three half-lives 1
• Diabetes indication: Consult endocrinology regarding risks/benefits of discontinuation and need for bridging therapy 1

High-Risk Factors for Aspiration with Semaglutide

• Recent initiation or dose increase
• Presence of gastrointestinal symptoms (nausea, vomiting, abdominal distention)
• Higher doses used for weight loss
• Co-prescribed medications that delay gastric emptying (opioids, PPIs, TCAs)

Common Pitfalls to Avoid

1. Insufficient discontinuation time for semaglutide: Multiple cases show aspiration risk even after holding for 6-7 days 1
2. Relying solely on fasting guidelines: Standard fasting times are inadequate for patients on semaglutide 1, 2
3. Failing to distinguish between indications: Patients taking semaglutide for weight loss may be at higher risk than those taking it for diabetes 1
4. Overlooking the need for airway protection: Even with prolonged fasting, patients on semaglutide require consideration for rapid sequence induction 1

In summary, while both medications should be discontinued before surgery, the risk of pulmonary aspiration with semaglutide presents a more immediate and potentially catastrophic complication compared to the metabolic risks associated with empagliflozin, making appropriate discontinuation of semaglutide the higher priority.