Metformin-Associated Lactic Acidosis: Bridging Pharmacokinetic Determinants, Metabolic Pathways, and Clinical Outcomes - PubMed
4 hours ago
- #Metformin-Associated Lactic Acidosis
- #Clinical Management
- #Pharmacokinetics
- Metformin is a first-line treatment for type 2 diabetes with a generally safe profile.
- A rare but serious side effect is metformin-associated lactic acidosis (MALA), characterized by high anion-gap metabolic acidosis, lactate >5 mmol/L, and arterial pH <7.35.
- MALA pathophysiology involves mitochondrial complex I inhibition, leading to altered redox states and reduced liver lactate clearance.
- It is primarily an accumulation disorder triggered by acute kidney function decline, not intrinsic metformin toxicity at therapeutic levels.
- Risk factors include acute or chronic kidney disease, liver impairment, sepsis, hypoxia, and dehydration.
- Early symptoms include metabolic acidosis, rapid breathing, low blood pressure, and mental status changes, requiring prompt diagnosis via blood gases, lactate, and renal tests.
- Management involves stopping metformin, supportive care, and renal replacement therapy in severe cases.
- Prevention focuses on patient selection, renal monitoring, dose adjustment, and temporary withdrawal during acute illnesses.
- Mortality from MALA is context-dependent, with timely interventions like extracorporeal therapy improving survival rates.