Why SGLT2 Inhibitors Must Be Suspended Before Surgery
SGLT2 inhibitors must be discontinued 3-4 days before elective surgery to prevent euglycemic diabetic ketoacidosis (euDKA), a potentially life-threatening complication that can occur even with normal blood glucose levels. 1
The Primary Risk: Euglycemic Diabetic Ketoacidosis
The critical danger is euDKA—a metabolic emergency where patients develop severe ketoacidosis despite having normal or near-normal blood glucose levels (often <250 mg/dL). 2 This occurs because:
SGLT2 inhibitors alter the insulin-glucagon ratio, decreasing insulin secretion while relatively increasing glucagon, creating a hormonal environment that promotes ketogenesis independent of glucose levels. 2
The clinical effects persist beyond plasma half-life, with urinary glucose excretion continuing for 3 days after discontinuation, and some cases showing effects lasting up to 2 weeks. 3
Surgical stress, prolonged fasting, and metabolic changes act as key triggers that amplify ketone production in the perioperative setting. 4, 5
Evidence-Based Discontinuation Timeline
The American Diabetes Association and American College of Cardiology recommend stopping SGLT2 inhibitors 3-4 days before elective surgery: 1, 2
- Canagliflozin, dapagliflozin, and empagliflozin: ≥3 days before surgery 1
- Ertugliflozin: ≥4 days before surgery 1
The FDA drug labels explicitly mandate withholding at least 3 days prior to procedures associated with prolonged fasting. 3
Alternative UK Approach
A more recent 2025 UK multidisciplinary consensus suggests a less conservative approach of omitting SGLT2 inhibitors only the day before and day of surgery (minimum 36-52 hour gap depending on timing). 1 However, this recommendation acknowledges that postoperative ketoacidosis has occurred even when patients withheld SGLT2 inhibitors for >72 hours, emphasizing that risk exists on a continuum. 1
Clinical Presentation Challenges
Euglycemic DKA is diagnostically treacherous because:
- Blood glucose appears reassuringly normal (<250 mg/dL), masking the severity of metabolic derangement. 2
- Patients present with metabolic acidosis (pH <7.3), elevated anion gap, decreased bicarbonate (<18 mEq/L), and elevated ketones despite normal glucose. 2
- Symptoms are nonspecific (nausea, vomiting, abdominal pain, malaise, shortness of breath) and can mimic surgical complications or acute abdomen. 5
Risk Stratification
Emergency surgery carries significantly higher risk than elective procedures (1.1% vs 0.17% incidence of perioperative ketoacidosis). 2, 6
High-risk patient populations include: 3, 7
- Those with pancreatic insulin deficiency (type 1 diabetes, history of pancreatitis or pancreatic surgery)
- Patients on very low-energy/liver reduction diets preoperatively
- Non-diabetic patients taking SGLT2 inhibitors for heart failure (they lack sufficient insulin reserve to prevent ketosis) 2
- Major surgical procedures triggering stronger stress responses 2
Critical Mitigation Strategies During Withholding Period
While SGLT2 inhibitors are held, implement these protective measures: 1, 2
- Maintain adequate hydration to prevent volume depletion and ketone generation 1, 2
- Avoid prolonged fasting periods—adhere strictly to recommended fasting guidelines 1
- Monitor glucose AND ketone levels during the perioperative period 1, 2
- Consider glucose-containing IV fluids in unavoidable prolonged fasting situations to mitigate ketone generation 1, 2
The Heart Failure Dilemma
A significant clinical challenge exists for patients taking SGLT2 inhibitors for heart failure: cessation may be associated with worsening heart failure. 1, 2 This creates a risk-benefit tension that requires:
- Shared decision-making discussions with patients about ketoacidosis risk versus heart failure decompensation 1
- Careful monitoring during the withholding period
- Balancing the competing risks of stopping medication early versus deferring surgery due to hyperglycemia 1
When to Restart SGLT2 Inhibitors
For outpatient surgery: Restart once eating and drinking normally, usually 24-48 hours postoperatively. 1
For inpatient surgery: Restart only when: 1
- Patient is eating and drinking normally
- Capillary ketones are <0.6 mmol/L
- Patient is clinically stable
Provide written sick-day rules at discharge instructing patients to stop SGLT2 inhibitors during acute illness. 1
Common Pitfalls to Avoid
- Don't rely solely on blood glucose monitoring—ketoacidosis can occur with normal glucose, so ketone monitoring is essential in high-risk patients. 2
- Don't assume 24-48 hours is sufficient—case reports document euDKA occurring even after 48-72 hours of discontinuation. 8, 5
- Don't forget non-diabetic patients—those taking SGLT2 inhibitors for heart failure or renal protection remain at risk. 2
- Don't restart prematurely—ensure clinical stability and normal oral intake before resuming therapy. 1, 3