How long should metformin (biguanide oral hypoglycemic agent) be withheld before surgery to minimize the risk of lactic acidosis in patients with impaired renal function?

Holding Metformin Before Surgery

Stop metformin the night before elective surgery (12-24 hours preoperatively) and do not restart until 48 hours after surgery, after confirming adequate renal function with eGFR ≥60 mL/min/1.73m². 1, 2, 3

Timing of Discontinuation

• For patients with normal renal function, discontinue metformin the night before surgery, which allows for adequate drug clearance given metformin's plasma half-life of 6.2 hours. 1, 2
• This 12-24 hour preoperative window is sufficient for significant drug elimination in patients without renal impairment. 3
• For emergency surgery, proceed without delay but monitor lactate levels and renal function closely throughout the perioperative period. 3, 4

Rationale: Risk of Lactic Acidosis

• Metformin-associated lactic acidosis (MALA) is rare (2-9 cases per 100,000 patients/year) but carries a catastrophic mortality rate of 30-50%. 5, 1, 4
• The primary mechanism is renal failure leading to metformin accumulation, which decreases hepatic lactate uptake and increases blood lactate levels. 4
• Surgery increases MALA risk through hemodynamic instability, perioperative fasting, volume depletion, and potential acute kidney injury. 3, 4

High-Risk Patients Requiring Extra Caution

Identify patients at increased risk for MALA before surgery:

• Renal impairment: Creatinine clearance <60 mL/min or eGFR <60 mL/min/1.73m² 5, 4
• Severe heart failure: Left ventricular ejection fraction <30% 5, 2
• Dehydration or fasting status 5, 2
• Concurrent medications: ACE inhibitors, ARBs, diuretics, or NSAIDs 5, 2
• Elderly patients (>65 years), who comprised 68% of lactic acidosis cases in French surveillance data 5
• Hepatic impairment, which reduces lactate clearance 4

When to Restart Metformin Postoperatively

Do not restart metformin until ALL of the following criteria are met:

• Minimum 48 hours have elapsed after major surgery 5, 1, 3
• Confirmed adequate renal function: eGFR ≥60 mL/min/1.73m² 1, 2, 3
• Patient is eating and drinking normally 3
• No ongoing hemodynamic instability (no vasopressor requirement) 1
• Absence of dehydration, acute heart failure, sepsis, or respiratory insufficiency 1

The 48-hour delay is critical because surgery-induced renal impairment may not be immediately apparent on postoperative day 1. 2

Special Surgical Considerations

• For iodinated contrast procedures: Stop metformin at the time of or prior to contrast administration in patients with eGFR 30-60 mL/min/1.73m², history of hepatic impairment, alcoholism, heart failure, or intra-arterial contrast use. Re-evaluate eGFR 48 hours later before restarting. 4
• For minor or ambulatory surgery: Guidelines suggest metformin may be continued except in cases of severe renal failure, though the conservative approach of stopping the night before remains standard practice. 5

Evidence Nuances

While recent research suggests that continuing metformin perioperatively may not significantly raise lactate levels or worsen outcomes 6, 7, 8, consensus guidelines from major societies (American College of Cardiology, American Heart Association, American Diabetes Association) maintain the recommendation to discontinue metformin due to the catastrophic consequences when MALA does occur. 1, 2, 3 The 2024 AHA/ACC guidelines acknowledge that recent data suggest metformin may not be as strongly associated with lactic acidosis as previously feared, but the conservative perioperative approach remains standard practice. 1, 2

Critical Pitfalls to Avoid

• Do not restart metformin at 24 hours postoperatively, even if renal function appears normal—wait the full 48 hours for major surgery. 1, 3
• Do not assume normal renal function without checking eGFR before restarting, as perioperative acute kidney injury may be subclinical. 2, 4
• Do not restart metformin in patients still requiring vasopressors or with ongoing volume depletion, regardless of timing. 1
• Do not confuse the 48-hour preoperative discontinuation recommendation (which is outdated and from manufacturer labeling) with current guideline recommendations of stopping the night before. 4, 9