Question

A 65 year old woman has been taking metformin for the past month to regulate her blood sugar. She frequently suffers from heartburn and occasionally takes a histamine receptor blocker (over-the-counter Tagamet (cimetidine), to relieve the heartburn. She tolerated Tagamet well, and never experienced any side effects.

She had her extended family over for Thanksgiving and having eaten much more than usual, she was taking Tagamet in maximal doses for well over a week. A few days after the Holiday, she was taken to the hospital because of profound weakness and confusion, where it was found that her blood creatinine was 0.7 mg/dL; her blood sugar was low and she developed metabolic acidosis (low blood pH and serum bicarbonate).

What caused hypoglycemia and acidosis in this patient?

Chose the correct answer:

1) Cimetidine alters the rate of glucuronidation of metformin in the liver, decreasing the proportion of the water-soluble metabolite of metformin available for excretion by the kidney. This decreases renal clearance of metformin and increases its blood concentration, resulting in adverse effects such as hypoglycemia and acidosis.

2) Cimetidine reduces renal clearance of metformin by inhibiting tubular secretion of metformin via the organic cation transporters. This increases blood concentration of metformin and contributes to development of adverse effects such as hypoglycemia and lactic acidosis.

3) Hypoglycemia and acidosis in this patient are most likely caused by impaired kidney function, which decreased clearance of metformin. Since 90% of metformin is excreted by the kidney, decreased kidney function and decreased clearance of metformin result in accumulation of metformin in the serum and lead to typical signs of metformin toxicity such as hypoglycemia and lactic acidosis.

Answer 1

Answer is option 3. Cimetidine reduces the renal clearance of metformin because it inhibits tubular secretion of metformin. This causes accumulation of metformin which causes toxicity signs like hypoglycaemia and lactic acidosis.