What are the most common metabolic derangements that cause type 2 lactic acidosis (Lactic Acidosis), specifically Hyperlactatemia?

From the Guidelines

Type 2 lactic acidosis is primarily caused by metabolic derangements such as diabetes mellitus with poor glycemic control, liver dysfunction, and medications like metformin. The most common metabolic derangements causing type 2 lactic acidosis include:

• Diabetes mellitus with poor glycemic control, which leads to increased lactate production through enhanced glycolysis 1
• Liver dysfunction, which prevents adequate lactate clearance since the liver is responsible for up to 70% of lactate metabolism
• Medications, particularly metformin, which inhibits mitochondrial complex I and can cause lactic acidosis, especially in patients with significant renal impairment or liver failure 1
• Other causes such as malignancies, thiamine deficiency, and mitochondrial disorders, which can also contribute to the development of type 2 lactic acidosis It is essential to note that metformin should be avoided in patients at risk for lactic acidosis, such as those with anaerobic metabolism, impaired metformin clearance, or impaired lactic acid clearance 1. Metformin should be discontinued if the estimated glomerular filtration rate (eGFR) is less than 30 mL/min per 1.73 m², and dose reduction is recommended if the eGFR is 30–45 mL/min per 1.73 m² 1. Lactate concentrations should be measured in fragile patients, and metformin should be withdrawn if increased lactate concentrations are apparent 1.

From the FDA Drug Label

There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases. Metformin associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate: pyruvate ratio; For each of the known and possible risk factors for metformin-associated lactic acidosis, recommendations to reduce the risk of and manage metformin-associated lactic acidosis are provided below: Renal impairment — The postmarketing metformin-associated lactic acidosis cases primarily occurred in patients with significant renal impairment Drug interactions —The concomitant use of metformin hydrochloride tablets with specific drugs may increase the risk of metformin-associated lactic acidosis: those that impair renal function, result in significant hemodynamic change, interfere with acid-base balance, or increase metformin accumulation Age 65 or greater —The risk of metformin-associated lactic acidosis increases with the patient's age because elderly patients have a greater likelihood of having hepatic, renal, or cardiac impairment than younger patients. Radiologic studies with contrast —Administration of intravascular iodinated contrast agents in metformin-treated patients has led to an acute decrease in renal function and the occurrence of lactic acidosis.

The most common metabolic derangements that cause type 2 lactic acidosis are:

• Renal impairment: Significant renal impairment is a primary risk factor for metformin-associated lactic acidosis.
• Drug interactions: Concomitant use of certain drugs that impair renal function, result in significant hemodynamic change, interfere with acid-base balance, or increase metformin accumulation.
• Age 65 or greater: Elderly patients have a greater likelihood of having hepatic, renal, or cardiac impairment, increasing the risk of lactic acidosis.
• Radiologic studies with contrast: Administration of intravascular iodinated contrast agents can lead to an acute decrease in renal function and the occurrence of lactic acidosis 2.

From the Research

Metabolic Derangements Causing Type 2 Lactic Acidosis

• Lactic acidosis is a common metabolic acidosis that can be caused by various factors, including diabetes mellitus 3
• The development of lactic acidosis is often associated with acute illness, particularly in patients with diabetes 4
• Metformin, an antihyperglycemic agent used in the treatment of type 2 diabetes mellitus, has been thought to cause lactic acidosis, but evidence suggests that diabetes rather than metformin therapy is the major risk factor for the development of lactic acidosis 4

Common Causes of Lactic Acidosis

• Acute cardiorespiratory illness
• Acute renal impairment
• Sepsis
• Diabetes mellitus 4
• Metformin use is not considered a major risk factor for lactic acidosis, but rather a factor that may contribute to its development in certain patients 5, 6, 7

Risk Factors for Lactic Acidosis

• Age 4
• Acute renal failure 4
• Sepsis 4
• Diabetes mellitus 4
• Metformin use in patients with chronic hypoxemic conditions, such as cardiovascular, renal, hepatic, and pulmonary disease, and advancing age 7