Tessa Quinn
Metformin is a commonly prescribed oral medication used to manage type 2 diabetes mellitus. Its use in hospitalized patients has been a subject of debate due to concerns about potential contraindications and precautions. The primary concern is the risk of metformin-associated lactic acidosis (MALA), especially with renal impairment, as metformin is renally cleared. Acute kidney injury (AKI) is a common inpatient condition, and the risk of MALA increases with declining renal function. However, the link between metformin and lactic acidosis has been disputed, and there is no proven risk of lactic acidosis in patients with normal kidney function. The use of metformin in hospitalized patients is further complicated by factors such as age, heart failure diagnoses, and the potential for unsafe contrast use during imaging procedures. While some guidelines recommend stopping metformin at hospital admission, others suggest it can be used in selected stable patients. The controversy surrounding metformin use in hospitals highlights the challenges physicians face in managing glucose levels in hospitalized patients with diabetes.
| Characteristics | Values |
|---|---|
| Risk of Lactic Acidosis | Increased with declining renal function |
| Renal Function | Metformin dosage reduction is recommended if the estimated glomerular filtration rate is 30 to 45 mL per minute per 1.73 m2 |
| Discontinuation | Recommended if the estimated glomerular filtration rate is less than 30 mL per minute per 1.73 m2 |
| Contrast Media-induced Nephropathy | Can decrease renal function and cause lactic acidosis |
| Inconsistent Guidelines | Some guidelines recommend stopping metformin before imaging procedures, while others indicate it can be used in selected stable patients |
| Poor Evidence | The evidence supporting recommendations is inconsistent |
| Inpatient Factors | Can increase the risk of renal or hepatic failure |
| Nonglycemic Benefits | Oral diabetes medications reduce the risk of fluctuating blood glucose levels |
| Safety | Can be used safely in many hospitalized patients with diabetes and normal kidney function |
| Age | Potentially unsafe for patients aged ≥65 years |
| Heart Failure | A diagnosis of heart failure is a precautionary warning |
| Acute Kidney Injury | A common inpatient condition that increases the risk of lactic acidosis |
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What You'll Learn
Metformin-associated lactic acidosis (MALA) risk
Metformin is a widely used and well-tolerated antidiabetic drug. However, in certain situations, its use may be paused (held) in hospital settings due to the risk of Metformin-associated lactic acidosis (MALA). MALA is a rare but life-threatening complication that can occur with metformin use, particularly in patients with impaired renal function. It is characterised by a pH of less than 7.35 and a lactate level greater than 5 mmol/L.
MALA occurs when metformin accumulates in the body to supra-therapeutic levels, leading to a reduction in lactate clearance and subsequent lactic acidosis. This can be caused by factors that decrease the renal elimination of metformin, such as renal impairment, the use of certain medications like histamine-2 receptor antagonists or ribociclib, and excessive alcohol consumption. Additionally, patients over the age of 65, those with heart failure, or those with chronic kidney disease are also at an increased risk of developing MALA.
The diagnosis of MALA requires careful exclusion of other causes of lactic acidosis, such as sepsis or hypoperfusion. Treatment involves the immediate cessation of metformin, supportive management, and addressing any underlying causes or coexisting conditions such as diabetic ketoacidosis. In severe cases, extracorporeal removal of metformin through hemodialysis or continuous kidney replacement therapy may be necessary.
The risk of MALA is particularly pertinent in hospital settings where patients may have multiple risk factors for developing lactic acidosis. In such cases, it is recommended to hold metformin and consider alternative treatments to ensure patient safety. This is especially important for critically ill patients in intensive care or high dependency units, where the presence of additional risk factors can further elevate the chances of developing MALA.
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Renal function and imaging procedures
The use of metformin in patients with renal dysfunction is controversial, and regulatory authorities have long imposed limitations on its use in such cases.
Metformin is contraindicated in patients with an eGFR (estimated glomerular filtration rate) of less than 30 mL/min/1.73 m2. If the eGFR is between 30 and 44 mL/min/1.73 m2, metformin treatment should be approached with caution, and a daily dose of ≤1,000 mg is recommended. When a patient's eGFR falls below 45 mL/min/1.73 m2, the benefits and risks of continuing treatment should be assessed.
The FDA has issued warnings regarding the use of metformin in patients with reduced kidney function. They recommend discontinuing the drug prior to iodinated contrast imaging procedures in patients with an eGFR between 30 and 60 mL/min/1.73 m2, and in those with a history of liver disease, alcoholism, or heart failure. Renal function should be reassessed 48 hours after the procedure, and metformin can be restarted if renal function is stable.
The use of metformin during computed tomography (CT) with radiocontrast agents is a particular area of concern due to the risk of contrast-induced nephropathy (CIN) and metabolic acidosis. However, there is a lack of clinical evidence to support discontinuing metformin in patients with normal renal function who undergo CT with minimal use of radiocontrast agents. The Royal College of Radiologists advises that there is no need to stop metformin after the use of radiocontrast agents. Nevertheless, the American College of Radiology recommends against metformin use in patients receiving contrast with an eGFR <30 mL/min/1.73 m2 or those with acute kidney injury or severe chronic kidney disease within 48 hours of undergoing imaging with contrast.
In summary, while the safety of metformin in patients with renal dysfunction is controversial, current guidelines suggest that it should be used cautiously or discontinued in certain cases, particularly when iodinated contrast imaging procedures are involved. Renal function should be monitored regularly, especially in patients at increased risk of renal impairment, and treatment decisions should be made on a case-by-case basis, considering the benefits and risks.
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Inpatient factors and renal/hepatic failure risk
Metformin is a commonly prescribed oral medication for the management of type 2 diabetes mellitus. However, its use in hospitalised patients is controversial due to the risk of metformin-associated lactic acidosis (MALA). Acute kidney injury (AKI) is a common inpatient condition, and metformin is renally cleared, so the risk of MALA increases with renal impairment. This has led to clinicians routinely holding metformin for all hospitalised patients.
While MALA is rare, the risk increases with declining renal function. Metformin dosage reduction is recommended if the estimated glomerular filtration rate is 30 to 45 mL per minute per 1.73 m2, and it should be discontinued if it falls below 30 mL per minute per 1.73 m2. Additionally, metformin use is contraindicated in patients with a documented diagnosis of heart failure or clinically significant hepatic impairment, further highlighting the importance of renal and hepatic function in metformin therapy.
Furthermore, inpatient factors can increase the risk of renal or hepatic failure. For example, uncontrolled blood glucose levels in hospitalised patients can negatively impact wound healing, increase the risk of infection, and delay surgical procedures or discharge. This complexity in glucose management, along with the potential for inpatient renal or hepatic complications, contributes to the cautious approach of holding metformin in hospitalised patients.
However, it is important to note that there is limited evidence evaluating the safety and efficacy of metformin in hospitalised patients. While multiple guidelines recommend stopping metformin at hospital admission, oral diabetes medications like metformin offer important nonglycemic benefits and help stabilise blood glucose levels. The decision to hold metformin should be carefully considered, weighing the risks of MALA and renal/hepatic failure against the benefits of maintaining glycaemic control and preventing fluctuations in blood glucose levels.
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Blood glucose targets and insulin regimens
Metformin is held in hospitals due to contraindications and precautions. For example, if the patient is over 65, has heart failure, or has received contrast imaging within the past 48 hours.
People with diabetes should aim for a blood glucose level between 4 and 7 mmol/L before meals, and less than 8 mmol/L two hours after meals. The closer to 'normal' (3.5-5.5 mmol/L before meals), the better.
If your blood glucose levels are not within your target range, you may need to adjust your insulin dosage. If you are on a basal bolus insulin regimen, you should monitor your blood glucose levels more frequently: before meals, before bed, before driving, and occasionally in the middle of the night. This will help you and your doctor assess your overnight insulin needs.
If you are on a twice-daily insulin mixture, you should initially test your blood glucose four times a day: before each meal and before bed. This will help determine the best insulin dose for you. Subsequently, you can alternate the timing of these tests: before breakfast and dinner one day, and before lunch and bedtime the next.
If you are taking a long-acting or intermediate-acting insulin, and it does not lower your blood glucose sufficiently, you may need to take another type of insulin that works more quickly. This is usually taken before meals. If you need both intermediate and rapid-acting insulin, your doctor may recommend a mixed insulin (biphasic insulin) instead of separate injections. This reduces the number of injections but is less flexible.
If you have type 2 diabetes, your doctor will usually prescribe insulin if other diabetes medications are no longer effective in keeping your blood glucose within a healthy range. Insulin helps your body use glucose for energy and reduces the risk of hyperglycaemia and long-term complications that can damage your heart, kidneys, eyes, and nerves.
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Patient age and medical history
Metformin is a medication used to control type 2 diabetes. It is the preferred initial pharmacologic treatment for type 2 diabetes due to its efficacy in controlling blood glucose levels and reducing the risk of cardiovascular events and death. While metformin is a valuable medication for managing diabetes, its use may be temporarily discontinued or held in certain situations, especially when patients are hospitalized.
Patient age is a crucial factor in determining whether to hold metformin during hospitalization. Studies have shown that older age, particularly above 65 years, is one of the most common reasons for potentially unsafe metformin use. Elderly patients are more susceptible to age-related kidney problems, which can increase the risk of metformin-associated complications, such as lactic acidosis. Therefore, healthcare providers may decide to hold metformin for older patients in the hospital setting to mitigate these risks.
The presence of specific medical conditions in a patient's history can also influence the decision to hold metformin during hospitalization. Metformin use is associated with an increased risk of lactic acidosis, especially in patients with a history of heart failure, liver disease, kidney disease, or acute kidney injury. Additionally, patients with a history of heart attacks, strokes, diabetic ketoacidosis, comas, or other medical conditions may be advised to refrain from taking metformin during their hospital stay. Holding metformin in these cases is a precautionary measure to reduce the likelihood of adverse events.
Furthermore, patients' medical histories regarding medication use and procedures are essential considerations. If a patient is scheduled for surgery or a medical procedure, metformin is typically held to reduce the risk of dehydration and metabolic complications. Additionally, the concurrent use of certain medications with metformin may increase the risk of lactic acidosis. Therefore, it is crucial to inform healthcare providers about any other prescription or non-prescription medications, vitamins, supplements, or herbal products being taken. This information helps them make informed decisions about holding or adjusting metformin during hospitalization.
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Frequently asked questions
Metformin is an oral medication used in the management of type 2 diabetes mellitus. Hospitals may hold metformin due to the risk of metformin-associated lactic acidosis (MALA), which increases with renal impairment. Acute kidney injury (AKI) is a common inpatient condition, and metformin is renally cleared, so the risk of MALA increases with renal impairment.
Precautionary warnings for holding metformin include:
- Lactic acidosis, defined as blood lactate concentration >4.0 mEq/L, arterial blood pH <7.35, and electrolyte disturbances leading to an increased anion gap.
- Unsafe contrast use, which is defined as receiving contrast with an eGFR <30 mL/min/1.73 m2 or in patients with acute kidney injury or severe chronic kidney disease.
- Age greater than 65 years.
- Diagnosis of heart failure.
- Clinically significant hepatic impairment.
- Chronic kidney disease.
Holding metformin in hospitals can help reduce the risk of renal or hepatic failure, which are common inpatient factors. Uncontrolled blood glucose levels can lead to negative effects on wound healing, an increased risk of infection, and delays in surgical procedures or discharge.
