Do I need to stop taking Synjardy (empagliflozin and metformin) prior to surgery?

Perioperative Management of Synjardy (Empagliflozin/Metformin)

Yes, you must stop Synjardy at least 3 days before surgery due to the empagliflozin (SGLT2 inhibitor) component, and hold metformin the night before surgery. 1, 2

Timing of Discontinuation

SGLT2 Inhibitor Component (Empagliflozin)

• Discontinue empagliflozin 3-4 days before surgery to reduce the risk of perioperative euglycemic diabetic ketoacidosis (DKA), a serious and potentially life-threatening complication 1, 2
• The FDA label for Synjardy explicitly states: "Withhold SYNJARDY or SYNJARDY XR at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting" 2
• This 3-4 day window is critical because SGLT2 inhibitors have been associated with euglycemic DKA in the perioperative period, where patients develop metabolic acidosis with ketones but blood glucose levels remain deceptively normal (<14 mmol/L or 250 mg/dL) 3

Metformin Component

• Stop metformin the night before surgery (on the day of surgery) 1, 4
• The 2024 AHA/ACC guidelines and American Diabetes Association both recommend holding metformin on the day of surgery 1
• While older concerns about lactic acidosis have been somewhat tempered by recent evidence, the consensus remains to hold metformin perioperatively due to potential surgical stress, renal impairment, and hemodynamic instability 4

Clinical Rationale

Why SGLT2 Inhibitors Must Be Stopped

• Euglycemic DKA is difficult to diagnose because blood glucose levels appear reassuringly normal, leading to delayed recognition and treatment 3
• Case reports document euglycemic DKA occurring after cardiac surgery in patients who stopped SGLT2 inhibitors only 1-2 days preoperatively, demonstrating that shorter discontinuation periods are insufficient 3
• The mechanism involves increased ketogenesis combined with surgical stress, fasting, and insulin deficiency, all while glucose levels remain misleadingly normal 3

Why Metformin Should Be Held

• Surgical stress can cause transient renal impairment that may not be immediately apparent on laboratory testing 4
• Perioperative hemodynamic instability, dehydration, and tissue hypoperfusion increase the theoretical risk of metformin accumulation and lactic acidosis 4
• The plasma half-life of metformin is 6.2 hours, so stopping the night before allows adequate clearance 4

Practical Algorithm for Synjardy Discontinuation

For elective surgery:

1. Stop Synjardy 3-4 days before surgery (this satisfies both the SGLT2 inhibitor requirement and exceeds the metformin requirement) 1, 2
2. Check renal function (eGFR) before surgery 4
3. Assess volume status and correct any depletion before surgery 2
4. Monitor blood glucose every 2-4 hours while NPO and use short/rapid-acting insulin as needed 1
5. Consider reducing basal insulin by 25% the evening before surgery to prevent hypoglycemia 1

For emergency surgery:

• Proceed with surgery but monitor lactate levels and renal function closely 4
• Be vigilant for signs of euglycemic DKA postoperatively (nausea, vomiting, tachypnea, anion gap metabolic acidosis with pH <7.3) 3

When to Restart Synjardy After Surgery

Metformin Component

• Do not restart metformin until 48 hours after surgery 4
• Confirm adequate renal function (eGFR ≥60 mL/min/1.73m²) before restarting 4
• Ensure the patient is eating well and clinically stable 4
• Do not restart if patient has ongoing dehydration, vasopressor requirement, acute heart failure, sepsis, or respiratory insufficiency 4

SGLT2 Inhibitor Component

• Do not restart empagliflozin until the patient is clinically stable and has resumed a normal diet 4
• Ensure resolution of any surgical stress and confirmation of stable renal function 4

Critical Pitfalls to Avoid

• Do not assume normal blood glucose rules out DKA in patients who recently took SGLT2 inhibitors—check serum and urine ketones if metabolic acidosis is present 3
• Do not restart metformin at 48 hours if renal function has not been verified—surgery can cause transient renal impairment 4
• Do not stop Synjardy only 1-2 days before surgery—this is insufficient for the SGLT2 inhibitor component and increases euglycemic DKA risk 3
• Do not use correction-only insulin perioperatively—basal-bolus insulin coverage improves outcomes compared to reactive sliding scale alone 1

Special Considerations

• The 2024 AHA/ACC guidelines note that recent data suggest metformin may not be as strongly associated with lactic acidosis as previously feared, but the conservative approach of holding it perioperatively remains standard practice 1, 4
• Patients with renal impairment (eGFR <60 mL/min/1.73m²) require even more cautious management and longer discontinuation periods 4
• The combination of surgical fasting, stress, and SGLT2 inhibitor effects creates a perfect storm for ketoacidosis, making the 3-4 day discontinuation window non-negotiable 3