Is a patient with a history of lactic acidosis secondary to Metformin (metformin) at increased risk of recurrence, making it a contraindication to restarting Metformin (metformin) after correction of lactic acidosis?

From the Guidelines

Metformin should not be restarted in patients who have previously developed metformin-associated lactic acidosis (MALA), as the risk of recurrent MALA outweighs the benefits of metformin therapy in these individuals. This recommendation is based on the understanding that patients who have experienced this serious adverse effect once are at higher risk for recurrence if rechallenged with the medication, as noted in a study published in The Lancet Diabetes and Endocrinology 1. The pathophysiology involves metformin's interference with mitochondrial function and lactate metabolism, particularly in patients with underlying risk factors such as renal impairment, hepatic dysfunction, or conditions that may cause tissue hypoxia.

Some key points to consider when managing patients with a history of MALA include:

• The risk of lactic acidosis is increased in patients with renal impairment, hepatic dysfunction, or conditions that may cause tissue hypoxia, as highlighted in a study published in Diabetes Care 1.
• Alternative glucose-lowering medications should be considered, such as SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, sulfonylureas, or insulin, depending on the patient's specific clinical situation and comorbidities.
• The risk of recurrent MALA, which carries a mortality rate of approximately 30-50%, outweighs the benefits of metformin therapy in these individuals, as noted in a study published in Circulation 1.
• 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, as highlighted in a study published in Diabetes Care 1.

Overall, the risk of recurrent MALA associated with metformin use in patients who have previously developed this condition is a significant concern, and alternative treatment options should be considered to minimize this risk.

From the Research

Lactic Acidosis and Metformin

• Lactic acidosis is a rare but serious complication associated with metformin use in the treatment of type 2 diabetes mellitus, with an overall mortality rate of approximately 50% 2.
• The development of lactic acidosis is often caused by preventable drug accumulation, and prevention is a key factor in reducing the risk of this complication 3.
• Metformin-associated lactic acidosis (MALA) typically occurs in patients with elevated plasma metformin concentrations, often due to renal impairment, and a secondary event or condition that disrupts lactate production or clearance, such as sepsis or hypoperfusion 4.

Contraindications to Restarting Metformin

• Patients who develop lactic acidosis secondary to metformin use are often considered to be at a contraindication to restarting metformin after the lactic acidosis has been corrected 4, 2.
• However, some studies suggest that the risk of lactic acidosis may be lower than previously thought, and that metformin can be safely used in patients with mild to moderate renal impairment 3, 5.
• The decision to restart metformin in a patient who has developed lactic acidosis should be made on a case-by-case basis, taking into account the individual patient's risk factors and medical history.

Risk Factors for Lactic Acidosis

• Renal impairment is a significant risk factor for the development of lactic acidosis in patients taking metformin, as it can lead to elevated plasma metformin concentrations 4, 5.
• Other risk factors for lactic acidosis include sepsis, hypoperfusion, and other conditions that disrupt lactate production or clearance 4.
• The use of metformin in patients with reduced kidney function has been shown to be associated with a higher risk of lactic acidosis hospitalization, although the absolute risk is still relatively low 5.