Does linagliptin (Dipeptidyl peptidase-4 inhibitor) need to be discontinued prior to surgery?

Perioperative Management of Linagliptin for Surgery

Linagliptin does not need to be discontinued prior to surgery and can be safely continued throughout the perioperative period. Unlike other antidiabetic medications that require discontinuation before surgery, linagliptin has a favorable pharmacokinetic profile that allows for its continued use.

Evidence-Based Recommendations for Linagliptin

The 2024 American Diabetes Association Standards of Care provides specific perioperative recommendations for various antidiabetic medications 1:

• SGLT2 inhibitors should be discontinued 3-4 days before surgery
• Metformin should be held on the day of surgery
• Other oral glucose-lowering agents should be held the morning of surgery

Notably, DPP-4 inhibitors like linagliptin are not included in the list of medications that require discontinuation. This represents a key distinction in perioperative management compared to other antidiabetic drug classes.

Pharmacological Rationale

Linagliptin has several unique pharmacological properties that support its continued use during the perioperative period:

• Minimal renal clearance: Unlike other DPP-4 inhibitors, linagliptin is primarily eliminated through the hepatobiliary system with only about 5% excreted in urine 2
• Long half-life: Terminal half-life >100 hours, allowing stable drug levels even with missed doses 2
• Low risk of hypoglycemia: DPP-4 inhibitors work in a glucose-dependent manner, significantly reducing hypoglycemia risk during periods of fasting 3
• No dose adjustment required: Linagliptin doesn't require dose adjustments based on renal or hepatic function 4

Contrast with Other Antidiabetic Medications

The perioperative management of linagliptin differs significantly from other diabetes medications:

• SGLT2 inhibitors: Must be discontinued 3-4 days before surgery due to risk of euglycemic diabetic ketoacidosis 1, 5
• Metformin: Should be held on the day of surgery 1
• GLP-1 receptor agonists: Should be discontinued at least one day before surgery (daily formulations) or >1 week (weekly formulations) due to delayed gastric emptying and aspiration risk 6

Perioperative Glycemic Management

When continuing linagliptin during the perioperative period:

1. Target perioperative blood glucose range of 100-180 mg/dL (5.6-10.0 mmol/L) 1
2. Monitor blood glucose every 2-4 hours while the patient is NPO 1
3. Supplement with short- or rapid-acting insulin as needed for glycemic control 1
4. Consider that linagliptin alone may be insufficient for glycemic control during surgical stress, and additional insulin may be required 1

Clinical Evidence

A randomized controlled trial with sitagliptin (another DPP-4 inhibitor) showed that continuing DPP-4 inhibitor therapy during cardiac surgery was associated with lower insulin requirements after transition to regular wards, without increasing complications 7. This supports the safety of continuing DPP-4 inhibitors like linagliptin during the perioperative period.

Potential Benefits of Continuing Linagliptin

• Maintains baseline glycemic control
• Reduces insulin requirements postoperatively
• Simplifies medication management
• Avoids potential hyperglycemia from medication discontinuation
• No risk of euglycemic ketoacidosis (unlike SGLT2 inhibitors)

Conclusion

Based on current guidelines and pharmacological properties, linagliptin can be safely continued throughout the perioperative period without discontinuation. This approach simplifies perioperative medication management while maintaining glycemic control with minimal risk of hypoglycemia.