Should metformin (biguanide oral hypoglycemic agent) be held in patients with type 2 diabetes mellitus (T2DM) undergoing surgery, particularly those with impaired renal function?

Should Metformin Be Held for Surgery?

Yes, metformin should be held on the day of surgery—specifically, stop it the night before elective surgery and do not restart until 48 hours postoperatively after confirming adequate renal function. 1, 2, 3

Timing of Metformin Discontinuation

• Stop metformin the night before elective surgery rather than the outdated 48-hour preoperative hold. 1, 2
• For emergency surgery, proceed without delay but monitor lactate levels and renal function closely if metformin is on board. 2, 3
• The FDA label explicitly states that metformin should be temporarily discontinued while patients have restricted food and fluid intake during surgical procedures. 4

When to Restart Metformin Postoperatively

Do not restart metformin until 48 hours after major surgery AND after confirming:

• Adequate renal function (eGFR ≥60 mL/min/1.73 m²) 3, 5
• Patient is eating and drinking normally 3
• No ongoing hemodynamic instability 3

For minor/ambulatory procedures, metformin can be restarted sooner once oral intake resumes and renal function is stable. 1

Rationale: Risk of Lactic Acidosis

The primary concern is metformin-associated lactic acidosis (MALA), which has a mortality rate of 30-50% when it occurs. 1, 3

Key risk factors that make surgery particularly dangerous:

• Perioperative fasting and fluid restriction leading to volume depletion 4
• Hemodynamic instability and hypoperfusion 4
• Acute kidney injury from surgical stress 1
• Tissue hypoxia and anaerobic metabolism 1
• Impaired lactate clearance due to hepatic hypoperfusion 4

While the absolute incidence of MALA is low (2-9 cases per 100,000 patient-years), the catastrophic consequences justify the conservative approach. 1, 3

High-Risk Patients Requiring Extra Caution

Identify patients at increased risk for MALA before surgery:

• Baseline renal impairment (eGFR <60 mL/min/1.73 m²) 1, 4
• Elderly patients (>65 years) with higher likelihood of organ impairment 1, 4
• Severe heart failure (LVEF <30%) 1
• Liver disease or alcoholism 1, 4
• Patients on ACE inhibitors, ARBs, diuretics, or NSAIDs 1
• Dehydration or sepsis 1

In these high-risk patients, metformin should be stopped earlier and restarted more cautiously. 1, 3

Evidence Nuances and Controversies

The evidence shows conflicting data:

• Some studies found no increase in lactic acidosis with continued perioperative metformin use. 6, 7
• One RCT showed continuation of metformin did not improve glucose control or raise lactate to clinically significant levels. 6
• Another study in CABG patients found metformin users actually had lower peak lactate levels than non-users. 7

However, major guidelines uniformly recommend discontinuation because:

• The studies showing safety were small and excluded high-risk patients 8, 9
• Cases of MALA in surgical patients have been documented, particularly with risk factors present 1
• The FDA label explicitly warns about surgery as a risk factor 4
• The consequences of MALA are catastrophic even if rare 1, 3

Practical Management Algorithm

Preoperatively:

• Stop metformin the night before elective surgery 1, 2
• Check baseline eGFR and identify risk factors 1, 3
• Ensure adequate hydration 3
• For emergency surgery, proceed but alert team to metformin use 2, 3

Intraoperatively:

• Maintain adequate perfusion and oxygenation 3
• Use balanced crystalloids for fluid resuscitation 3
• Monitor for tissue hypoperfusion 3

Postoperatively:

• Check renal function at 48 hours 1, 3
• Restart metformin only if eGFR ≥60 mL/min/1.73 m², patient eating/drinking normally, and hemodynamically stable 3, 5
• Monitor for signs of MALA (hyperventilation, abdominal pain, altered mental status) 4

Common Pitfalls to Avoid

• Don't restart metformin too early after major surgery—wait the full 48 hours and confirm renal function. 1, 3
• Don't forget to check eGFR before restarting—surgical stress can cause acute kidney injury. 3, 4
• Don't continue metformin in patients with eGFR <60 mL/min/1.73 m² who are having contrast studies or major surgery. 4
• Don't assume the patient stopped metformin—explicitly verify medication adherence preoperatively. 3