What are the perioperative considerations for patients with diabetes taking Sodium-Glucose Linked Transporter (SGLT) inhibitors and Glucagon-Like Peptide (GLP) receptor agonists undergoing surgery?

Perioperative Management of SGLT2 Inhibitors and GLP-1 Receptor Agonists

For SGLT2 inhibitors, discontinue the day before and day of surgery (minimum 36-52 hours depending on dosing schedule); for GLP-1 receptor agonists, hold weekly formulations for 3 weeks and daily formulations for 3-4 days before elective surgery to prevent life-threatening complications of ketoacidosis and pulmonary aspiration. 1, 2

SGLT2 Inhibitor Management

Preoperative Discontinuation Timeline

• Stop SGLT2 inhibitors the day before and the day of the procedure, which provides a minimum 36-hour gap if taken in the evening, or 48-52 hours if taken in the morning before a morning/afternoon procedure 1
• The American Diabetes Association recommends discontinuing SGLT2 inhibitors 3-4 days before surgery, though the 2025 UK multidisciplinary consensus accepts the shorter "day before" approach as pragmatic 3, 1
• For patients on very low-energy/liver reduction diets before bariatric or laparoscopic surgery, stop SGLT2 inhibitors at the commencement of the diet (typically 2-4 weeks preoperatively), as the combination creates severe ketoacidosis risk 1

Critical Risk: Euglycemic Ketoacidosis

• SGLT2 inhibitors cause ketoacidosis through increased renal glucose excretion, which triggers lipolysis and ketone production even with normal blood glucose levels 1
• Ketoacidosis can occur even when SGLT2 inhibitors are held for >72 hours, emphasizing that risk exists on a continuum without a defined safe threshold 1
• Emergency surgery patients have 6.5-fold higher ketoacidosis rates (1.1%) compared to elective surgery (0.17%) 1
• Euglycemic ketoacidosis now occurs in patients without diabetes mellitus taking SGLT2 inhibitors for heart failure or chronic kidney disease, requiring vigilance in all patients on these medications 1

Intraoperative and Postoperative Monitoring

• Maintain adequate hydration, avoid prolonged fasting periods, and monitor both glucose and ketones perioperatively 1
• Consider glucose-containing intravenous fluids during unavoidable prolonged fasting to mitigate ketone generation 1
• Restart SGLT2 inhibitors only when eating and drinking normally AND capillary ketones are <0.6 mmol/L (typically 24-48 hours postoperatively for outpatients) 1
• Provide written sick-day rules at preoperative assessment and discharge 1

Balancing Competing Risks

• Cessation of SGLT2 inhibitors in heart failure patients may worsen heart failure, requiring careful risk-benefit assessment 1
• The risk of perioperative hyperglycemia from stopping SGLT2 inhibitors must be weighed against ketoacidosis risk, though the latter is potentially fatal 1

GLP-1 Receptor Agonist Management

Preoperative Discontinuation Timeline

• Hold weekly GLP-1 receptor agonists (semaglutide, dulaglutide) for 3 weeks before elective surgery to allow clearance of approximately 88% of the drug based on three half-lives 2, 4
• Hold daily GLP-1 receptor agonists (liraglutide) for 3-4 days before surgery 2
• Discontinuation for only 1 week is inadequate, as studies demonstrate this shorter period does not decrease the prevalence of retained gastric contents 2, 4

Critical Risk: Pulmonary Aspiration

• GLP-1 receptor agonists significantly delay gastric emptying through inhibition of gastric peristalsis, increased pyloric tone, and vagal pathway activation 2, 4
• 24.2% of patients on semaglutide have residual gastric content compared to 5.1% of controls, even after 12+ hour fasting periods 2
• Multiple case reports document pulmonary aspiration requiring ICU admission in patients who fasted 18-20 hours and stopped semaglutide 4-6 days before surgery 2
• The American Diabetes Association acknowledges limited data on safe use and influence of GLP-1 receptor agonists on delayed gastric emptying perioperatively 3, 2

Distinction Between Diabetes and Weight Loss Indications

• For non-diabetic patients using GLP-1 receptor agonists for weight loss, hold for the full 3 weeks without exception, as risks of continuing outweigh any benefits 2, 4
• For diabetic patients, consult endocrinology to weigh glycemic control benefits against aspiration risk, as prolonged cessation may have detrimental effects on perioperative glycemic control 2, 4
• The benefits of glycemic control may outweigh delayed gastric emptying issues in diabetic patients, requiring individualized assessment 3, 2

Risk Mitigation When Adequate Holding Period Not Achieved

• Consider postponing elective procedures if medication has not been held for adequate duration 2, 4
• Perform point-of-care gastric ultrasound preoperatively to assess for residual gastric contents (target gastric volume <1.5 ml/kg) 2, 4, 5
• Administer prokinetic drugs (metoclopramide or erythromycin) preoperatively to enhance gastric emptying 2, 4, 5
• Implement rapid-sequence intubation with full airway protection rather than supraglottic airways, as case reports document aspiration with supraglottic devices 2, 4, 5
• Consider pre-emptive gastric decompression in very high-risk patients 2, 5

Preoperative Documentation Requirements

• Document indication and dose of GLP-1 receptor agonist, date commenced, dose variations, and last dose taken 2, 4
• Assess for symptoms of nausea, vomiting, or abdominal distention 2, 4
• Review co-prescribed drugs that delay gastric emptying (opioids, proton pump inhibitors, tricyclic antidepressants) 2
• Document recent recreational drug use that delays gastric emptying (alcohol, cannabis) 2
• Patients who recently started or increased their dose require extra caution and may need even longer discontinuation periods 2, 4

Perioperative Glycemic Management

Target Glucose Levels

• Perioperative blood glucose goal is 100-180 mg/dL (5.6-10.0 mmol/L) within 4 hours of surgery 3
• Stricter goals (<80 mg/dL) are not advised, as they do not improve outcomes and increase hypoglycemia risk 3
• A1C goal for elective surgeries should be <8% (<63.9 mmol/L) whenever possible 3

Other Antidiabetic Medication Management

• Hold metformin on the day of surgery 3
• Hold other oral glucose-lowering agents the morning of surgery 3
• Give one-half of NPH dose or 75-80% of long-acting analog insulin doses 3
• Reduce basal insulin by 25% the evening before surgery to achieve perioperative goals with lower hypoglycemia risk 3
• Monitor blood glucose at least every 2-4 hours while NPO and dose with short- or rapid-acting insulin as needed 3
• Basal-bolus insulin coverage is superior to correction-only insulin in noncardiac general surgery, with improved glycemic outcomes and lower complication rates 3

Intraoperative Monitoring

• CGM should not be used alone for glucose monitoring during surgery 3
• Use point-of-care blood glucose testing for intraoperative decisions 3

Common Pitfalls to Avoid

• Do not rely on standard fasting guidelines alone for patients on GLP-1 receptor agonists, as retained gastric contents persist despite extended fasting 2
• Do not assume one week of GLP-1 receptor agonist discontinuation is adequate, as emerging evidence demonstrates this is insufficient 2, 4
• Do not use supraglottic airway devices in patients who have not had adequate GLP-1 receptor agonist discontinuation 2, 4, 5
• Do not ignore ketoacidosis risk in non-diabetic patients on SGLT2 inhibitors, as euglycemic ketoacidosis now occurs in this population 1
• Do not restart SGLT2 inhibitors until ketones are <0.6 mmol/L, even if the patient is eating and drinking normally 1