Why is metformin (a biguanide oral hypoglycemic agent) not initiated in hospitalized patients with impaired renal function or other acute conditions?

From the Guidelines

Metformin should not be initiated in hospitalized patients due to the increased risk of lactic acidosis, particularly in those with compromised kidney function, which is common during acute illness. The primary concern is the risk of lactic acidosis, a rare but potentially fatal complication that can occur when metformin accumulates in patients with impaired renal function 1. Hospitalized patients often experience fluctuations in renal function due to their underlying conditions, procedures, or contrast studies, which further increases the risk of lactic acidosis with metformin. Additionally, many hospitalized patients are at risk for or already experiencing hypoxemia, hypoperfusion, or sepsis, all of which increase the risk of lactic acidosis with metformin 1.

Some key points to consider when managing diabetes in the hospital setting include:

• The risk of lactic acidosis with metformin is increased in patients with compromised kidney function, and the medication should be held at least 48 hours before and after procedures involving iodinated contrast 1
• Hospitalized patients often have unpredictable oral intake and may be NPO (nothing by mouth) for procedures, making oral medications like metformin problematic
• Insulin is the preferred agent for glycemic control in the hospital setting because it can be titrated precisely, works rapidly, and can be administered regardless of the patient's oral intake status or organ function
• Metformin therapy can typically be resumed once the patient is stable, eating regularly, and has demonstrated stable kidney function with an eGFR above 30 mL/min 1

It's also important to note that metformin is contraindicated in patients with advanced renal insufficiency and should be used with caution in patients with impaired hepatic function or congestive heart failure because of the increased risk of lactic acidosis 1. The American Diabetes Association recommends that metformin be avoided in unstable or hospitalized patients with heart failure 1.

In terms of specific guidelines, the American Journal of Kidney Diseases recommends that metformin not be given to patients with serum creatinine concentrations of 1.5 mg/dL or greater in men and 1.4 mg/dL or greater in women because it is cleared by the kidney and may build up with even modest impairment of kidney function, putting patients at risk of lactic acidosis 1. However, the most recent study from 2021 suggests that metformin can be used safely in patients with estimated glomerular filtration rate ≥30 mL/min/1.73 m², but with caution and close monitoring of lactate levels 1.

Overall, the decision to initiate metformin in a hospitalized patient should be made on a case-by-case basis, taking into account the patient's individual risk factors and medical history. However, in general, it is recommended to avoid initiating metformin in hospitalized patients due to the increased risk of lactic acidosis and other safety concerns.

From the FDA Drug Label

1. 3 Recommendations for Use in Renal Impairment Assess renal function prior to initiation of metformin hydrochloride tablets and periodically thereafter. Metformin hydrochloride tablets are contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m 2. Initiation of metformin hydrochloride tablets in patients with an eGFR between 30 to 45 mL/minute/1. 73 m 2is not recommended.
2. 6 Renal Impairment Metformin is substantially excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of renal impairment. Metformin hydrochloride tablets are contraindicated in severe renal impairment, patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m 2

Metformin should not be started in patients in the hospital due to the potential risk of lactic acidosis and renal impairment. Hospitalized patients may have unstable renal function, and metformin is contraindicated in patients with an eGFR below 30 mL/min/1.73 m2 2. Additionally, metformin should be used with caution in patients with hepatic impairment 2. It is essential to assess renal function prior to initiation of metformin and periodically thereafter to minimize the risk of adverse effects 2.

From the Research

Reasons for Not Starting Metformin in Hospitalized Patients

• Metformin is associated with a risk of lactic acidosis, particularly in patients with chronic kidney disease or acute kidney injury 3, 4, 5, 6, 7
• Lactic acidosis can be a life-threatening condition with high mortality rates, especially if not recognized and treated promptly 4, 7
• The risk of lactic acidosis is increased in patients with conditions that reduce metformin renal clearance, such as sepsis, fever, diarrhea, and vomiting 3
• Hospitalized patients may be more likely to have these conditions, making it safer to avoid starting metformin until their condition stabilizes
• Additionally, metformin should be used with caution in patients with chronic kidney disease, and the dosage should be adjusted based on the level of kidney function 6

Key Considerations for Metformin Use

• Patients should be aware of the risks of lactic acidosis and the importance of discontinuing metformin in case of acute illness or kidney injury 3, 6
• Healthcare providers should closely monitor renal function and adjust metformin dosage accordingly 6
• In cases of lactic acidosis, prompt treatment with hemodialysis or continuous renal replacement therapy is crucial to improve survival and correct acidosis 3, 4, 5, 7