Should Metformin Be Stopped to Avoid Lactic Acidosis?
Metformin should NOT be routinely stopped in all patients to avoid lactic acidosis, but must be discontinued when eGFR falls below 30 mL/min/1.73 m² and temporarily withheld during acute illnesses that compromise renal function, contrast procedures in at-risk patients, and perioperative periods with restricted oral intake. 1
Risk Context: Lactic Acidosis is Extremely Rare
The actual incidence of metformin-associated lactic acidosis (MALA) is extraordinarily low at less than 1 per 100,000 patient-years 2, with some large analyses showing 2-9 cases per 100,000 patient-years 3. A Cochrane meta-analysis of 347 studies found zero cases of lactic acidosis in 55,451 metformin patient-years 3. This means the absolute risk is negligible in appropriately selected patients, and the cardiovascular and mortality benefits of metformin far outweigh this minimal risk in most clinical scenarios. 3
When to Continue Metformin Safely
Normal to Mild Renal Impairment (eGFR ≥45 mL/min/1.73 m²)
- Continue metformin at standard doses without interruption 3, 4
- Monitor eGFR every 3-6 months 4
- No dose adjustment needed 2
Moderate Renal Impairment (eGFR 30-44 mL/min/1.73 m²)
- Continue metformin with dose reduction 3, 2
- Do NOT initiate metformin in this range, but existing therapy can continue 1
- Increase monitoring frequency to every 3-6 months 3, 4
- Evidence shows reduced 2-year mortality compared to other glucose-lowering therapies even in this range 3
When Metformin MUST Be Stopped
Absolute Contraindications (Permanent Discontinuation)
- eGFR <30 mL/min/1.73 m² (CKD stages 4-5) 3, 2, 1
- Clinical or laboratory evidence of hepatic disease 1
- Acute or chronic metabolic acidosis 1
Temporary Discontinuation Required ("Sick-Day Rules")
Stop metformin immediately during:
- Any acute illness causing dehydration (fever, vomiting, diarrhea) 2, 1
- Serious intercurrent illness increasing AKI risk in patients with eGFR <60 mL/min/1.73 m² 3
- Cardiovascular collapse, acute MI, sepsis, or conditions with hypoxemia 1
- Acute congestive heart failure with hypoperfusion 1
Perioperative Management:
- Stop metformin the night before surgery 3
- Do not restart for 48 hours after major surgery and only after confirming stable renal function 3
- For minor/ambulatory surgery, may continue unless severe renal failure present 3
Contrast Procedures:
- Stop metformin at time of or prior to iodinated contrast in patients with eGFR 30-60 mL/min/1.73 m², history of liver disease, alcoholism, heart failure, or intra-arterial contrast administration 1
- Re-evaluate eGFR 48 hours post-procedure before restarting 1
- However, the 2014 ESC guidelines note there is "no convincing evidence" for routine suspension in all patients, and checking renal function after angiography with selective discontinuation only if function deteriorates is an acceptable alternative 3
Common Pitfall: Overly Conservative Cessation
The most common error is stopping metformin unnecessarily in stable patients with mild-to-moderate renal impairment (eGFR 30-60 mL/min/1.73 m²). 3, 5 This deprives patients of metformin's proven cardiovascular benefits and mortality reduction 3. The Swedish National Diabetes Register showed reduced mortality risk even in patients with eGFR 30-45 mL/min/1.73 m² 3.
Recognizing True MALA
If lactic acidosis occurs, confirm MALA by:
- Arterial pH <7.35 3
- Blood lactate >5 mmol/L (45 mg/dL) 3, 1
- Detectable plasma metformin concentration 3
- Anion gap acidosis without ketonuria 1
Management requires immediate metformin discontinuation and urgent hemodialysis (metformin clearance up to 170 mL/min), which is highly effective at reversing symptoms 1, 6, 7.
Patient Education Essentials
All patients on metformin must understand to temporarily stop the medication during: