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Perioperative Timing for Stopping Oral Hypoglycemic Agents and Insulin

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Preoperative Target

• HbA1c should be checked within 3 months of surgery
• Consider postponing elective surgery if HbA1c > 8-9% (due to increased risk of infection and poor wound healing)
• Do not delay urgent/emergency surgery solely for elevated HbA1c
• Perioperative glucose target: 140-180 mg/dL (ADA); some guidelines accept up to 180 mg/dL
• Avoid hypoglycemia - it is more dangerous than mild perioperative hyperglycemia

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Oral Hypoglycemic Agents (OHAs)

1. Sulfonylureas (glipizide, glibenclamide, glimepiride, glyburide)

• Reason: Risk of prolonged hypoglycemia during the fasting period; symptoms masked under anesthesia

2. Metformin (Biguanide)

• Traditional reason: Risk of lactic acidosis with hypovolemia, renal dysfunction, and iodinated contrast
• Evolving evidence (2026): Large population studies have NOT demonstrated a significantly increased risk of lactic acidosis in metformin users. Recent cardiovascular and perioperative guidelines suggest continuing metformin throughout the perioperative period is reasonable in many stable patients with normal renal function. The NYSORA 2026 review (citing Riesemann et al., Curr Opin Anaesthesiol 2026) notes this shift toward individualized risk-based management
• Bottom line: Many centers now continue metformin for minor/elective procedures in low-risk patients; hold it for major surgery, procedures with contrast, or patients with renal impairment

3. Thiazolidinediones (pioglitazone, rosiglitazone)

• Low hypoglycemia risk; however, associated with fluid retention - relevant in cardiac patients
• Most older guidelines say they may be continued; newer individualized approach applies

4. SGLT2 Inhibitors (empagliflozin, dapagliflozin, canagliflozin, ertugliflozin)

• Reason: Risk of euglycemic diabetic ketoacidosis (eDKA) - blood glucose may appear near-normal, making diagnosis easily missed. Presents with nausea, vomiting, abdominal pain, tachypnea, metabolic acidosis
• The FDA safety labeling mandates at least 3 days discontinuation; most current guidelines use 3-4 days
• Important: Stop SGLT2 inhibitors even for minor surgical procedures

5. DPP-4 Inhibitors (sitagliptin, saxagliptin, linagliptin, alogliptin)

• Low intrinsic hypoglycemia risk; generally safe but typically withheld while the patient is fasting
• Some institutions continue them perioperatively for minor procedures

6. GLP-1 Receptor Agonists (semaglutide, liraglutide, dulaglutide, exenatide)

• Primary concern: Delayed gastric emptying increases risk of residual gastric contents and potential pulmonary aspiration
• Evolving evidence (2025-2026): A large 2025 meta-analysis (>185,000 patients) showed increased residual gastric contents in GLP-1 users but no statistically significant increase in aspiration events. Another study (~600,000 patients) showed actually lower observed aspiration rates in GLP-1 users vs. non-users
• Current guideline position: Most current international guidelines still support holding GLP-1 RAs as above, but acknowledge the evidence is shifting toward individualized risk assessment; if GLP-1 RA was not held as recommended, consider point-of-care gastric ultrasound or modified RSI
• Note: GLP-1 RAs also used for obesity/weight management (e.g., Ozempic, Wegovy) - same hold rules apply

7. Meglitinides (repaglinide, nateglinide)

• Very short-acting; risk of hypoglycemia if taken without food intake

8. Alpha-glucosidase inhibitors (acarbose, miglitol)

• Rarely cause hypoglycemia alone; hold simply because they need carbohydrate intake to work

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Insulin - Perioperative Timing

Type 1 Diabetes

• Never omit basal insulin entirely - these patients will develop DKA without any insulin
• Give 1/2 to 2/3 of usual intermediate-acting (NPH) insulin on the morning of surgery
• Alternative: Run an insulin infusion at 0.5-2 units/hour titrated to blood glucose
• Co-administer 5% dextrose at 75-125 mL/hour to prevent hypoglycemia during the fast
• Regular insulin sliding scale (RISS) can supplement but should not be used as the sole control method

Type 2 Diabetes - Insulin Users

• Perioperative glucose control: insulin infusion titrated to blood glucose OR basal long-acting insulin + RISS
• RISS as the sole control method is discouraged - leads to wide glucose fluctuations
• Check blood glucose every 1-2 hours intraoperatively

Insulin Pumps (CSII)

• Discuss with the patient and endocrinology team before surgery
• For short cases, the pump may be continued at the basal rate
• For longer or complex procedures, convert to IV insulin infusion

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Summary Table

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Key 2024-2026 Updates (vs. Older Guidelines)

1. SGLT2 inhibitors - The 3-4 day hold is now firmly established across all major guidelines (SAMBA 2024, ADA 2026) due to eDKA risk
2. GLP-1 RAs - The 1-week hold for weekly formulations is now standard, though emerging data challenge the aspiration risk concern; individualized decisions are replacing blanket rules
3. Metformin - The knee-jerk "hold for 24-48 h" rule is being challenged; continuation is now considered reasonable in many patients with normal renal function
4. Glucose targets - The ADA endorses 140-180 mg/dL perioperatively; avoiding hypoglycemia remains the priority
5. HbA1c threshold - Most guidelines suggest delaying elective surgery if HbA1c > 8-8.5%, but this is not absolute

Oral Hypoglycemic Agents - Perioperative Timing

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Insulin - Perioperative Dose Adjustments

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Key Rules to Remember