A 58-year-old woman has been prescribed cimetidine for the treatment of gastroesophageal reflux. She has tried two other proton pump inhibitors previously, but they have not eased her symptoms. You check her medical record and notice that she is also on metformin. What is the most likely interaction between cimetidine and metformin?

• A. Increased risk of lactic acidosis
• B. Decreased metformin effectiveness
• C. Reduced gastric acidity
• D. No interaction

Answer: (A)

The key idea is that metformin is cleared by the kidneys through specific transporters, and certain drugs can block those transporters. Metformin relies on uptake into renal tubular cells via the OCT2 transporter and then on the MATE1/2 transporters to be secreted into the urine. Cimetidine can inhibit these transporters, so metformin is cleared more slowly. This raises metformin levels in the blood, and metformin-associated lactic acidosis, though rare, is a serious risk especially if kidney function is not optimal. So the most likely interaction is an increased risk of lactic acidosis due to higher metformin exposure.

The other options don’t fit as well. Reducing gastric acidity doesn’t affect metformin’s action or clearance in a meaningful way, so reduced acidity isn’t the interaction of concern. Decreased effectiveness isn’t typical with this mechanism, and saying there’s no interaction ignores the transporter-mediated effect that raises risk.