Why withhold metformin (biguanide oral hypoglycemic agent) when a patient is unwell?

From the Guidelines

Metformin should be temporarily discontinued in patients with type 2 diabetes when they are unwell, particularly if they are experiencing vomiting, diarrhea, or any condition causing dehydration, as it can increase the risk of lactic acidosis due to compromised kidney function or dehydration 1. This practice is often referred to as the "sick day rule" and is recommended to prevent the accumulation of metformin in the bloodstream, which can occur when the body is under stress from illness, altering kidney function and metabolism. Additionally, dehydration from vomiting or diarrhea reduces blood flow to the kidneys, further impairing metformin clearance. Some key points to consider when withholding metformin in unwell patients include:

• Monitoring blood glucose levels more frequently during the temporary discontinuation of metformin
• Resuming metformin once the patient is eating and drinking normally, typically after 24-48 hours of recovery
• Contacting the healthcare provider if illness persists beyond 24 hours or if blood glucose levels remain consistently high (above 270 mg/dL or 15 mmol/L)
• Considering alternative glucose-lowering strategies as directed by the healthcare provider during the temporary discontinuation of metformin. It is also important to note that metformin may be used safely in individuals with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m², but lower doses may be used in those with an eGFR 30–45 mL/min/1.73 m², and it is contraindicated in those with advanced renal insufficiency 1.

From the FDA Drug Label

Surgery and other procedures —Withholding of food and fluids during surgical or other procedures may increase the risk for volume depletion, hypotension, and renal impairment. Metformin hydrochloride tablets should be temporarily discontinued while patients have restricted food and fluid intake Hypoxic states —Several of the postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure (particularly when accompanied by hypoperfusion and hypoxemia) When such an event occurs, discontinue metformin hydrochloride tablets.

Metformin should be withheld when a patient is unwell, especially in situations that may lead to hypoxia, volume depletion, or renal impairment. This is because these conditions may increase the risk of lactic acidosis, a potentially life-threatening complication of metformin therapy 2.

• Key considerations include:
  • Hypoxic states, such as acute congestive heart failure or cardiovascular collapse
  • Surgery or other procedures that involve withholding food and fluids
  • Volume depletion or renal impairment, which may increase the risk of lactic acidosis It is essential to temporarily discontinue metformin hydrochloride tablets in these situations to minimize the risk of lactic acidosis.

From the Research

Withholding Metformin When Unwell

• Metformin is a commonly used medication for type 2 diabetes, but it can cause lactic acidosis, a potentially life-threatening condition, especially in patients with renal impairment 3, 4, 5, 6, 7.
• The risk of lactic acidosis is increased in patients with acute kidney injury, hypoxemia, sepsis, alcohol abuse, liver failure, myocardial infarction, and shock 6.
• Studies have shown that metformin-associated lactic acidosis can be prevented by discontinuing the medication in patients who are unwell, especially those with renal impairment or other risk factors 3, 6.
• Continuous renal replacement therapy (CRRT) has been shown to be effective in treating metformin-associated lactic acidosis by removing metformin and its metabolites from the body and correcting acidosis and electrolyte imbalances 4, 5.
• The decision to withhold metformin in unwell patients should be based on individual assessment of the risk of lactic acidosis and the potential benefits of continuing the medication 6, 7.
• Patients with renal impairment should have their renal function monitored regularly, and the dose of metformin should be adjusted or discontinued if necessary to prevent lactic acidosis 7.

Key Factors to Consider

• Renal function: patients with renal impairment are at increased risk of lactic acidosis 3, 6, 7.
• Acute kidney injury: patients with acute kidney injury are at increased risk of lactic acidosis 4, 5, 6.
• Other risk factors: patients with hypoxemia, sepsis, alcohol abuse, liver failure, myocardial infarction, and shock are at increased risk of lactic acidosis 6.
• Dose and duration of metformin: high doses and prolonged use of metformin increase the risk of lactic acidosis 7.