Which substances interact with metformin?

• A. Aspirin and ibuprofen
• B. Vitamin C and zinc
• C. Ethanol and cimetidine
• D. Calcium carbonate and magnesium hydroxide

Answer: (C)

Metformin is cleared by the kidneys, so substances that affect renal clearance or increase lactate production can raise its risk of adverse effects. Ethanol is a known risk because alcohol can increase lactate production and, especially with reduced kidney function or dehydration, worsen lactic acidosis associated with metformin. Cimetidine can inhibit renal tubular secretion of metformin, leading to higher blood levels of the drug and a greater chance of lactic acidosis. Together, these interactions are the most clinically important with metformin, which is why this combination is highlighted.

Other substances listed don’t have as strong or direct a interaction with metformin in typical practice.