When Metformin is Contraindicated
Metformin is absolutely contraindicated when eGFR falls below 30 mL/min/1.73 m², in patients with decompensated liver disease, during acute illness or hospitalization, and in conditions predisposing to lactic acidosis such as severe heart failure or hypoxic states. 1
Absolute Contraindications Based on Renal Function
The FDA mandates that metformin cannot be used when eGFR is below 30 mL/min/1.73 m² due to the risk of metformin accumulation and lactic acidosis. 1 This is the most critical threshold to remember.
Renal Function Algorithm:
- eGFR ≥45 mL/min/1.73 m²: Metformin can be used with standard dosing and monitoring every 3-6 months 2, 3
- eGFR 30-45 mL/min/1.73 m²: Do not initiate metformin; if already on it, reassess benefit-risk and consider dose reduction or discontinuation 2, 1
- eGFR <30 mL/min/1.73 m²: Absolute contraindication—discontinue immediately 1
A critical pitfall: The older FDA guidance used serum creatinine cutoffs (≥1.5 mg/dL in men, ≥1.4 mg/dL in women), but the 2016 revision shifted to eGFR-based criteria, which is more accurate across different ages, weights, and races. 2 Always use eGFR, not creatinine alone.
Liver Disease Contraindications
Metformin is contraindicated in decompensated cirrhosis (Child-Pugh class B or C) because impaired hepatic function reduces lactate clearance, dramatically increasing lactic acidosis risk. 4, 1
Liver Disease Algorithm:
- Compensated cirrhosis (Child-Pugh A) with eGFR ≥45: Metformin can be used safely with monitoring every 3-6 months 4
- Decompensated cirrhosis (Child-Pugh B-C): Absolute contraindication regardless of renal function 4
- Acute hepatic dysfunction: Discontinue metformin immediately 1
The American Association for the Study of Liver Diseases emphasizes that even in compensated cirrhosis, metformin must be stopped if kidney function deteriorates below eGFR 45 mL/min/1.73 m². 4
Acute Illness and Hospitalization
Metformin must be discontinued during any hospitalization or acute illness that could compromise renal or hepatic function. 2, 5 This is a frequently missed contraindication in clinical practice.
Conditions Requiring Immediate Discontinuation:
- Any hospitalization (default position should be to stop metformin on admission) 5
- Sepsis or serious infections 4
- Dehydration from vomiting, diarrhea, or reduced oral intake 2, 4
- Acute heart failure with hypoperfusion or hypoxemia 4
- Acute kidney injury 5
- Conditions causing tissue hypoxia 2
The Lancet Diabetes and Endocrinology guidelines explicitly state that hospitalized patients face dynamic conditions that can rapidly create lactic acidosis risk factors, making continuation dangerous even if baseline renal function was adequate. 5
Contrast Imaging Procedures
Metformin must be temporarily discontinued before iodinated contrast procedures in specific high-risk patients. 1
Contrast Procedure Algorithm:
- eGFR 30-60 mL/min/1.73 m²: Stop metformin at time of or before procedure; restart only after confirming stable renal function 48 hours post-procedure 1
- History of liver disease, alcoholism, or heart failure: Stop metformin regardless of eGFR 1
- Intra-arterial contrast administration: Stop metformin regardless of eGFR 1
- eGFR >60 with no risk factors: Metformin can generally be continued, though some institutions adopt a universal stop policy 1
Cardiac Conditions
Metformin is contraindicated in acute or decompensated heart failure with hypoperfusion or hypoxemia. 2, 4 However, stable, compensated heart failure is not an absolute contraindication, though caution is warranted. 2
The KDOQI guidelines note that in studies of patients with comorbid conditions like congestive heart failure, lactic acidosis remained exceedingly rare when metformin was used with appropriate renal function monitoring. 2 The key distinction is between acute/unstable (contraindication) versus chronic/stable (use with caution).
Metabolic Acidosis
Metformin is contraindicated in any form of acute or chronic metabolic acidosis, including diabetic ketoacidosis. 1 This is an absolute contraindication regardless of other factors.
Hypoxic States
Any condition causing tissue hypoxia contraindicates metformin use. 2 This includes:
Alcohol Abuse
Chronic alcohol abuse is a contraindication to metformin because alcohol impairs hepatic lactate metabolism and increases lactic acidosis risk. 2, 1
Special Populations
Elderly Patients:
Advanced age alone is not a contraindication, but elderly patients require more frequent renal function monitoring (every 3-6 months) because age-related decline in kidney function is common. 3, 1 The American Diabetes Association notes that metformin dose selection in elderly patients should start at the low end of the dosing range. 1
Pregnancy:
Metformin should not be used during pregnancy according to the American Diabetes Association guidelines for type 2 diabetes in children and adolescents, which emphasizes the importance of preconception counseling. 2 Insulin is the preferred agent during pregnancy.
Common Clinical Pitfalls
Using serum creatinine instead of eGFR: Always calculate eGFR, as creatinine levels can be misleading in elderly, low-muscle-mass, or obese patients 2
Forgetting to stop metformin during acute illness: Educate patients on "sick-day rules"—hold metformin when acutely ill at home with vomiting, diarrhea, or reduced oral intake 4
Continuing metformin during hospitalization: The default should be discontinuation on admission unless there is a compelling reason to continue with daily monitoring 5
Not reassessing when eGFR falls to 30-45 range: This requires active decision-making about continuation, not passive continuation 2, 1
Assuming stable heart failure is an absolute contraindication: While acute/decompensated heart failure contraindicates metformin, stable compensated heart failure can be managed with metformin if renal function is adequate 2, 6