Metformin rarely causes hypoglycemia when used as monotherapy. The pharmacologic reason is:

• A It has an extremely short plasma half-life
• B It lowers glucose without stimulating insulin secretion ✓
• C It simultaneously stimulates glucagon release
• D It blocks insulin receptors after glucose normalizes

Explanation

Metformin activates AMP kinase, reducing hepatic gluconeogenesis and increasing peripheral glucose uptake and utilization. It is an antihyperglycemic rather than a true hypoglycemic agent because it does not drive insulin release from beta cells. When glucose falls toward normal, hepatic output is not suppressed below physiologic needs. Half-life is irrelevant to this property, and metformin neither raises glucagon nor blocks insulin receptors.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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