Which factor increases risk for metformin-associated lactic acidosis?

• A. Renal impairment
• B. High-protein diet
• C. Regular aerobic exercise
• D. Hydration

Answer: (A)

The main concept is that metformin clearance depends on the kidneys, so any reduction in renal function allows metformin to accumulate in the body. When metformin builds up, it can impair mitochondrial respiration in cells, pushing metabolism toward increased lactate production. If lactate accumulates, especially when clearance is compromised, metformin-associated lactic acidosis can occur. Hydration helps maintain kidney perfusion and drug elimination, which reduces risk, while factors like regular aerobic exercise or a high-protein diet don’t raise the risk in the context of metformin therapy. In short, renal impairment is the factor that increases the risk because it limits the drug’s clearance and promotes lactate buildup.