When should metformin (biguanide oral hypoglycemic agent) be withheld before surgery?

When to Withhold Metformin Before Surgery

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

Timing of Discontinuation

For Elective Surgery

• Discontinue metformin the evening before surgery for patients with normal renal function, allowing adequate clearance given metformin's 6.2-hour plasma half-life 1, 2
• For patients with baseline renal impairment (eGFR 30-60 mL/min/1.73m²), stop metformin at least 24-48 hours before the procedure 3
• Metformin is contraindicated in patients with eGFR <30 mL/min/1.73m² and should already be discontinued 3

For Emergency Surgery

• Proceed with surgery without delay if metformin cannot be stopped in advance 1, 2
• Alert the surgical and anesthesia team to metformin use 2
• Monitor lactate levels and renal function closely perioperatively 1, 2
• Ensure adequate fluid resuscitation with balanced crystalloids and maintain mean arterial pressure ≥65 mmHg 2
• Be prepared for hemodialysis if metformin-associated lactic acidosis (MALA) develops 3

Rationale for Withholding

Risk of Lactic Acidosis

• Metformin-associated lactic acidosis is rare (2-9 cases per 100,000 patients/year) but carries 30-50% mortality 1, 2
• Surgery increases MALA risk through multiple mechanisms: hemodynamic instability, perioperative fasting, tissue hypoperfusion, acute kidney injury, and volume depletion 1, 2, 3
• The FDA label mandates withholding metformin when food and fluid intake are restricted during surgical procedures 3

High-Risk Surgical Situations

Metformin must be stopped for procedures involving:

• Iodinated contrast administration (stop at time of or prior to procedure if eGFR 30-60 mL/min/1.73m², history of liver disease, alcoholism, heart failure, or intra-arterial contrast use) 4, 3
• Major abdominal surgery (higher risk of hemodynamic instability and acute kidney injury) 2
• Any procedure requiring prolonged NPO status 3

Criteria for Restarting Metformin

Do not restart metformin until ALL of the following criteria are met at 48 hours post-surgery: 1, 2, 3

• eGFR ≥60 mL/min/1.73m² (recheck renal function before restarting)
• Patient is eating and drinking normally
• No ongoing hemodynamic instability
• No dehydration, vasopressor requirement, acute heart failure, sepsis, or respiratory insufficiency
• No signs of lactic acidosis (normal lactate, no unexplained metabolic acidosis)

Why 48 Hours?

• Surgery can cause transient renal impairment not immediately apparent on laboratory testing 1
• Perioperative hemodynamic instability increases metformin accumulation risk even with seemingly normal renal function 1
• Metformin is substantially excreted by the kidney, and any degree of renal impairment increases accumulation risk 3

Special Populations Requiring Extra Caution

Higher risk patients who warrant more conservative management: 1, 3

• Age ≥65 years (assess renal function more frequently; age ≥80 requires documented normal kidney function before any metformin use) 3
• Baseline renal impairment (eGFR 30-60 mL/min/1.73m²)
• Congestive heart failure requiring treatment 3
• Liver disease or alcoholism 3
• Patients on ACE inhibitors, ARBs, or diuretics (increase MALA risk) 2

Common Pitfalls to Avoid

• Do not restart metformin at 48 hours if the patient has any ongoing clinical instability, even if creatinine appears normal—surgery-induced renal impairment may be delayed 1
• Do not assume normal preoperative renal function means safe continuation—the surgical stress itself creates risk 2, 3
• For procedures with contrast, remember to stop metformin even in patients with normal renal function if they have heart failure, liver disease, or alcoholism 3
• Recent evidence suggests metformin may not be as strongly associated with lactic acidosis as previously feared, but conservative perioperative management remains the standard of care given the catastrophic consequences of MALA 1, 2

Practical Algorithm Summary

Preoperatively:

• Stop metformin the night before elective surgery 1, 2
• Check baseline eGFR 3
• Ensure adequate hydration 2

Intraoperatively:

• Use balanced crystalloids for fluid resuscitation 2
• Maintain adequate perfusion (MAP ≥65 mmHg) 2

Postoperatively:

• Check renal function at 48 hours 1, 2
• Restart metformin only if eGFR ≥60 mL/min/1.73m², patient eating/drinking normally, and no clinical instability 1, 2, 3
• Monitor for MALA symptoms (weakness, muscle pain, respiratory distress, abdominal symptoms, hypothermia, bradycardia) 3