Should metformin be discontinued in a patient with lactic acidosis?

Should Metformin Be Held in Lactic Acidosis?

Yes, metformin must be discontinued immediately in any patient presenting with lactic acidosis. 1

Immediate Management

• Discontinue metformin immediately upon diagnosis or strong suspicion of lactic acidosis, as this is both a symptomatic and etiological treatment priority 1, 2
• The FDA drug label explicitly states that "if metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of metformin" 1
• Patients and families should be educated to discontinue metformin and report to their healthcare provider if symptoms of lactic acidosis occur (unexplained hyperventilation, myalgias, malaise, unusual somnolence) 1

Why Metformin Must Be Stopped

• Metformin decreases liver uptake of lactate, thereby increasing blood lactate levels and perpetuating the acidosis 1
• The drug is substantially excreted by the kidney, and in the setting of acute illness with lactic acidosis, renal function is often compromised, leading to metformin accumulation 1, 3
• Metformin plasma levels >5 mcg/mL are characteristic of metformin-associated lactic acidosis (MALA), and continued use will only worsen drug accumulation 1

Definitive Treatment Considerations

• Prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin, as metformin is dialyzable with clearance up to 170 mL/min under good hemodynamic conditions 1
• Hemodialysis has often resulted in reversal of symptoms and recovery in severe cases 1, 4
• For severe MALA, either intermittent hemodialysis or continuous kidney replacement therapy should be initiated 4

Clinical Context and Risk Factors

The relationship between metformin and lactic acidosis is complex—metformin may be causal, co-responsible, or coincidental 5. However, in the acute setting of established lactic acidosis, this distinction is less important than immediate action:

• Acute conditions predisposing to lactic acidosis where metformin should be discontinued include cardiogenic or distributive shock, sepsis, hypoxia, acute kidney injury, and dehydration 2, 6
• In hospitalized patients at risk for lactic acidosis (anaerobic metabolism from sepsis/hypoxia, impaired metformin clearance from renal impairment, or impaired lactate clearance from liver failure), metformin should be avoided 2
• A recent study in COVID-19 patients showed metformin use was associated with increased lactic acidosis incidence (adjusted HR 4.46), particularly with higher doses, worse kidney function, and greater disease severity 2

Common Pitfalls to Avoid

• Do not continue metformin while attempting to treat lactic acidosis with supportive measures alone—the drug itself contributes to lactate accumulation 1
• Do not delay discontinuation while waiting for metformin levels to return from the laboratory; clinical suspicion based on elevated lactate (>5 mmol/L), anion gap acidosis, and metformin use is sufficient 1, 4
• Awareness is insufficient among both patients and clinicians—many patients continue metformin in high-risk situations when temporary discontinuation causes no harm 6

When to Consider Restarting Metformin

After resolution of the acute episode, metformin should not be restarted until:

• Lactic acidosis has completely resolved and lactate levels have normalized 4
• Hemodynamic stability is confirmed without vasopressor support 7
• Renal function is stable with at least two consistent measurements showing eGFR ≥30 mL/min/1.73m² 7, 8
• The patient is clinically stable and has resumed normal diet 7
• Recheck kidney function post-recovery from critical illness before restarting 4

The direct metformin-related mortality when appropriately managed is close to zero, but failure to discontinue the drug in the setting of lactic acidosis can be fatal 5, 9.