Does an SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitor need to be held 3 days before elective surgery in patients taking it for heart failure?

SGLT2 Inhibitors Should Be Withheld 3-4 Days Before Elective Surgery Even When Used for Heart Failure

SGLT2 inhibitors should be withheld for 3-4 days before elective surgery regardless of whether they are being taken for diabetes or heart failure, to reduce the risk of perioperative metabolic acidosis. 1

Rationale for Withholding SGLT2 Inhibitors

• The American College of Cardiology/American Heart Association 2024 guidelines explicitly recommend that SGLT2 inhibitors should be withheld for 3-4 days before elective noncardiac surgery in patients with heart failure to reduce the risk of perioperative metabolic acidosis 1
• Specific recommendations include stopping canagliflozin, dapagliflozin, and empagliflozin ≥3 days and ertugliflozin ≥4 days before scheduled surgery 1
• The risk of perioperative diabetic ketoacidosis (DKA) is higher in patients taking SGLT2 inhibitors compared to those not taking them (1.02 vs. 0.69 per 1000 patients) 1
• SGLT2 inhibitors can cause euglycemic DKA regardless of whether the patient has diabetes, as they alter the insulin/glucagon ratio and predispose patients to ketosis 2

Mechanism of Risk

• SGLT2 inhibitors cause euglycemic DKA through altered insulin-glucagon ratios, leading to decreased insulin secretion and increased glucagon, creating a hormonal environment that promotes ketogenesis despite normal glucose levels 3
• The effects of SGLT2 inhibitors persist beyond their plasma half-life, with clinical effects continuing for 3-4 days after discontinuation 3
• Surgical stress, prolonged fasting, and metabolic changes associated with surgery are considered key triggers for SGLT2 inhibitor-induced ketoacidosis 4
• There are reports of postoperative ketoacidosis occurring even when patients have withheld SGLT2 inhibitors for >72 hours, emphasizing that the risk exists as a continuum rather than having a defined threshold 1

Alternative Approaches and Considerations

• UK guidelines suggest a less conservative approach, recommending omission of SGLT2 inhibitors the day before and the day of a procedure 1
• This would equate to at least a 48-hour gap (or 52+ hours for afternoon procedures) if the drug is taken in the morning 1
• Data suggest that cessation of SGLT2 inhibitors in people receiving them for heart failure may be associated with worsening of heart failure, creating a clinical dilemma 1, 3
• A study showed that approximately 29% of patients with heart failure required a reduction in loop diuretic dose within 60 days following SGLT2 inhibitor initiation, suggesting these medications have meaningful diuretic effects 5

Risk Mitigation Strategies

• If an SGLT2 inhibitor cannot be stopped for the recommended period, postoperative monitoring of anion gap and serum ketones can help detect clinically significant euglycemic DKA 6
• Maintaining adequate hydration, avoiding prolonged fasting periods, and monitoring glucose and ketone levels are important mitigations during the time of withholding SGLT2 inhibitors 1
• In settings of unavoidable prolonged fasting, consider glucose-containing intravenous fluids to mitigate ketone generation 1
• SGLT2 inhibitors should be restarted once the patient is eating and drinking normally (usually 24-48 hours after surgery) 1

Special Considerations

• Emergency surgery carries a higher risk of DKA than elective surgery (1.1% vs. 0.17%) 1, 3
• A significant interaction between hold time and emergency surgery has been observed in research, suggesting even greater caution is needed in emergency situations 6
• Non-diabetic patients taking SGLT2 inhibitors for heart failure are still at risk of euglycemic DKA, as they may not have sufficient insulin to prevent significant ketosis 1, 3
• For patients staying in hospital after surgery, consider restarting SGLT2 inhibitors once eating and drinking normally and capillary ketones are <0.6 mmol/L 1

Despite the potential concern about temporarily discontinuing SGLT2 inhibitors in heart failure patients, the risk of perioperative metabolic acidosis outweighs the short-term risk of heart failure exacerbation, making the 3-4 day withholding period the safest approach for elective surgery.