Metformin side effects lactic acidosis
Searched over 200M research papers
Research Analysis by Consensus
Beta · 18 papersConsensus Meter
Yes%
Possibly%
No%
Metformin Side Effects: Lactic Acidosis
Introduction to Metformin and Its Use in Diabetes Management
Metformin is a widely prescribed medication for the management of type 2 diabetes mellitus (T2DM). It is favored for its efficacy in lowering blood glucose levels and its relatively low risk of causing hypoglycemia compared to other antidiabetic agents. However, despite its benefits, metformin has been associated with a rare but serious side effect: lactic acidosis.
Understanding Lactic Acidosis
Lactic acidosis is a condition characterized by the buildup of lactate in the body, leading to an excessively low pH in the bloodstream. This can result in severe metabolic acidosis, which is potentially life-threatening. The condition is defined by an arterial lactate level greater than 5 mmol/L and an arterial blood pH of less than 7.35.
Incidence and Risk Factors of Metformin-Associated Lactic Acidosis (MALA)
Incidence Rates
The incidence of metformin-associated lactic acidosis (MALA) is notably low. Studies have reported an incidence rate of approximately 6.3 per 100,000 patient-years. Another comprehensive review found no significant increase in the risk of lactic acidosis in patients treated with metformin compared to those on other antidiabetic therapies.
Risk Factors
Several factors increase the risk of developing MALA. These include:
- Renal Impairment: Patients with chronic kidney disease (CKD) are at higher risk because impaired renal function can lead to the accumulation of metformin, thereby increasing lactate production .
- Hepatic Dysfunction: The liver plays a crucial role in lactate clearance. Hepatic impairment can exacerbate the risk of lactic acidosis .
- Cardiovascular and Pulmonary Diseases: Conditions that cause hypoxemia can predispose patients to lactic acidosis.
- Acute Illnesses: Situations such as sepsis, dehydration, and acute kidney injury can precipitate MALA .
Mechanism of Metformin-Induced Lactic Acidosis
Metformin inhibits mitochondrial respiration, particularly in the liver, leading to increased anaerobic glycolysis and lactate production. This inhibition occurs through the specific blockade of mitochondrial complex I, which impairs adenosine triphosphate (ATP) production and promotes lactate accumulation.
Clinical Presentation and Management
Symptoms
Patients with MALA typically present with nonspecific symptoms such as dizziness, lightheadedness, nausea, vomiting, and generalized weakness. Severe cases may involve profound hypotension, acute respiratory failure, and multiple organ dysfunction .
Diagnosis
Diagnosis is based on clinical presentation and laboratory findings, including high anion gap metabolic acidosis, elevated blood lactate levels, and low serum bicarbonate levels.
Treatment
The primary treatment for MALA involves supportive care and the correction of acidosis. Hemodialysis is often required to remove both lactate and metformin from the bloodstream, especially in severe cases . Early recognition and intervention are critical to improving patient outcomes.
Conclusion
While metformin is an effective and commonly used medication for T2DM, it carries a rare risk of lactic acidosis, particularly in patients with predisposing conditions such as renal or hepatic impairment. The incidence of MALA is low, but the condition is serious and requires prompt medical attention. Physicians should carefully monitor patients on metformin, especially those with risk factors, to mitigate the potential for this adverse effect.
Sources and full results
Most relevant research papers on this topic