Why withhold metformin (metformin) when a patient is unwell?

From the Guidelines

Metformin should be temporarily stopped during periods of acute illness, particularly when experiencing vomiting, diarrhea, or any condition causing dehydration, as it can increase the risk of lactic acidosis when a patient is dehydrated or has compromised kidney function due to illness. This practice, often called the "sick day rule," is recommended because metformin can accumulate in the bloodstream when the body is under stress, potentially leading to lactic acidosis 1. During illness, dehydration from vomiting or diarrhea reduces blood flow to the kidneys, further impairing metformin clearance. Lactic acidosis, though rare, is a serious condition with high mortality rates. Patients should resume metformin once they are eating and drinking normally and the acute illness has resolved, typically after 24-48 hours of recovery. If diabetes control becomes problematic during this temporary discontinuation, patients should contact their healthcare provider for guidance on alternative diabetes management strategies. Key considerations include monitoring kidney function and adjusting the metformin dose accordingly, as well as being aware of the potential risks of lactic acidosis in patients with compromised kidney function or other comorbidities 1.

Some of the key points to consider when managing metformin use in patients with acute illness include:

• Temporarily stopping metformin during periods of acute illness to reduce the risk of lactic acidosis
• Monitoring kidney function and adjusting the metformin dose accordingly
• Being aware of the potential risks of lactic acidosis in patients with compromised kidney function or other comorbidities
• Resuming metformin once the acute illness has resolved and the patient is eating and drinking normally
• Contacting the healthcare provider for guidance on alternative diabetes management strategies if diabetes control becomes problematic during the temporary discontinuation of metformin.

It is essential to prioritize the patient's safety and adjust the metformin dose or temporarily discontinue it as needed to minimize the risk of lactic acidosis and other complications 1.

From the FDA Drug Label

In patients taking metformin hydrochloride tablets whose eGFR falls below 45 mL/min/1. 73 m 2, assess the benefit and risk of continuing therapy. 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.

Withholding metformin when unwell is recommended in certain situations, including:

• Surgery and other procedures where food and fluids are withheld, as this may increase the risk of volume depletion, hypotension, and renal impairment.
• Hypoxic states, such as acute congestive heart failure, particularly when accompanied by hypoperfusion and hypoxemia.
• Renal impairment, where the eGFR falls below 45 mL/min/1.73 m^2, as the risk of metformin accumulation and metformin-associated lactic acidosis increases with the severity of renal impairment 2.

It is essential to temporarily discontinue metformin in these situations to minimize the risk of lactic acidosis and other adverse effects 2.

From the Research

Withholding Metformin When Unwell

• Metformin is a commonly used medication for type 2 diabetes, but it can lead to lactic acidosis, a potentially life-threatening condition, especially in patients with renal impairment or other risk factors 3, 4, 5.
• The risk of lactic acidosis is increased when metformin is taken in the presence of concomitant diseases or situations such as sepsis, fever, diarrhea, vomiting, which reduce metformin renal clearance 3.
• Studies have shown that lactic acidosis almost always develops because of preventable drug accumulation, and prevention is a key factor 3, 4, 6, 7.
• Patients should be aware that discontinuation of metformin for a limited time does not affect their health, but it may avoid a serious, potentially fatal adverse event 3.
• Treatment of metformin-associated lactic acidosis involves immediate cessation of metformin, supportive management, and extracorporeal removal of metformin with either intermittent hemodialysis or continuous kidney replacement therapy in severe cases 4, 6, 7.

Risk Factors for Lactic Acidosis

• Risk factors for metformin-associated lactic acidosis include:
  • Renal impairment or acute kidney injury 3, 4, 5
  • Sepsis, fever, diarrhea, vomiting 3
  • Liver disease, heart failure, or other metabolic disturbances 7
  • Excessive alcohol consumption 4
  • Histamine-2 receptor antagonists, ribociclib 4

Management of Lactic Acidosis

• Management of metformin-associated lactic acidosis is primarily supportive, with aggressive interventions including decontamination and extracorporeal treatments such as continuous renal replacement therapy (CRRT) to reverse acidosis and clear metformin metabolites 4, 6, 7.
• Early identification and initiation of extracorporeal treatment are crucial in managing severe metabolic acidosis and improving patient outcomes 7.