What is the primary mechanism of action of metformin?

Correct answer: C. It DECREASES hepatic gluconeogenesis and increases peripheral insulin sensitivity

• A. This is the opposite of metformin's action and is a distractor built into the recall source. Increasing gluconeogenesis would RAISE blood glucose.
• B. Alpha-glucosidase inhibition is the mechanism of acarbose and miglitol.
• C. CORRECT. Metformin (a biguanide) works chiefly by SUPPRESSING hepatic glucose production (gluconeogenesis), with secondary improvement in peripheral insulin sensitivity in muscle and reduced intestinal glucose absorption. Because it does not stimulate insulin secretion, metformin alone essentially does NOT cause hypoglycemia — an important point for chairside risk assessment. Its rare serious adverse effect is lactic acidosis, particularly in renal impairment. Common side effects: GI upset, metallic taste, B12 malabsorption.
• D. Insulin secretagogue activity describes SULFONYLUREAS (glipizide, glyburide) — these DO cause hypoglycemia and are the ones that matter for chairside emergencies.

Note: Metformin DECREASES it. Metformin-only patients are at low hypoglycemia risk; sulfonylurea and insulin patients are the ones to worry about.