What is the mechanism of metformin-associated lactic acidosis risk?

• A. Metformin inhibits mitochondrial respiration, and risk increases with renal impairment or conditions predisposing to lactic acidosis.
• B. Metformin increases hepatic gluconeogenesis
• C. Metformin causes metabolic alkalosis
• D. Metformin increases insulin production

Answer: (A)

The key idea is that metformin can impair cellular energy production by blocking mitochondrial respiration, which shifts metabolism toward anaerobic pathways and increases lactate formation. Because metformin is cleared by the kidneys, any renal impairment or conditions that predispose to poor lactate clearance (dehydration, hypoperfusion, liver disease, sepsis) allow the drug to accumulate and amplify this effect, raising the risk of lactic acidosis. Other choices don’t fit because metformin does not increase hepatic gluconeogenesis, does not cause metabolic alkalosis, and does not increase insulin production in a way that would explain lactic acidosis.