What is the treatment for metformin (biguanide)-associated lactic acidosis?

From the Guidelines

Treatment of metformin-associated lactic acidosis requires immediate discontinuation of metformin and aggressive supportive care, with the cornerstone of treatment being hemodialysis to effectively remove both metformin and lactate while correcting acid-base disturbances. The management of metformin-associated lactic acidosis (MALA) involves several key steps, including:

• Discontinuation of metformin, as its accumulation in the body can lead to inhibition of mitochondrial respiration and increased lactate production 1
• Fluid resuscitation with isotonic crystalloids to restore intravascular volume and improve tissue perfusion
• Sodium bicarbonate administration for severe acidosis (pH < 7.1) to help buffer excess acid, although its use remains controversial
• Hemodialysis, which is the most effective method for removing both metformin and lactate while correcting acid-base disturbances
• Continuous renal replacement therapy (CRRT) can be used in hemodynamically unstable patients
• Vasopressors like norepinephrine may be required for persistent hypotension
• Mechanical ventilation should be considered for patients with respiratory failure
• Blood glucose monitoring is essential, as hypoglycemia can occur when metformin is discontinued It is essential to note that metformin should be avoided in patients at risk for lactic acidosis, such as those with anaerobic metabolism (e.g., sepsis, hypoxia), impaired metformin clearance (significant renal impairment), or impaired lactic acid clearance (liver failure) 1. Early recognition and aggressive intervention are critical, as mortality rates can exceed 30% in severe cases.

From the FDA Drug Label

If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of metformin hydrochloride tablets In metformin hydrochloride tablets treated patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin hydrochloride is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions).

Treatment of Metformin-Associated Lactic Acidosis:

• Discontinue metformin: Immediately stop metformin hydrochloride tablets if lactic acidosis is suspected.
• General supportive measures: Institute general supportive measures promptly in a hospital setting.
• Hemodialysis: Prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin. 2 2 2

From the Research

Treatment of Metformin-Associated Lactic Acidosis

• The treatment of metformin-associated lactic acidosis (MALA) involves immediate cessation of metformin, supportive management, and treating other concurrent causes of lactic acidosis like sepsis 3.
• Severe MALA requires extracorporeal removal of metformin with either intermittent hemodialysis or continuous kidney replacement therapy 3, 4, 5.
• Prolonged hemodialysis should be considered as an early treatment option in cases of severe lactic acidosis due to massive metformin ingestion 4.
• Continuous renal replacement therapy has been suggested as a method for resolving this extremely dangerous metabolic state, with lactate levels decreasing to near zero within 7-19 hours in most patients 6.
• The optimal time to restart metformin has not been well-studied, but it is reasonable to first ensure that lactic acidosis has resolved, and then recheck the kidney function post-recovery from critical illness, ensuring that the estimated glomerular filtration rate is 30 mL/min/1.73 m2 or better before restarting metformin 3.

Role of Dialysis in Treatment

• Dialysis may be beneficial in preventing a higher mortality rate in patients with MALA who require renal replacement therapy 7.
• Hemodialysis was beneficial in preventing a higher mortality rate in those who required renal replacement therapy, although the mortality rate of patients who received dialysis was similar to that of patients who were not dialyzed 7.
• Prolonged intermittent hemodialysis may be an effective treatment option for metformin intoxication complicated by lactic acidosis and acute kidney injury 5.