A 58-year-old man with type 2 diabetes mellitus has an HbA1c of 8.5% despite lifestyle modifications. The physician chooses metformin as first-line therapy. The primary mechanism by which metformin lowers blood glucose is:

• A Activation of AMP-activated protein kinase (AMPK) reducing hepatic gluconeogenesis ✓
• B Stimulation of pancreatic beta-cell insulin secretion via SUR1 receptor closure
• C Inhibition of intestinal alpha-glucosidase delaying carbohydrate absorption
• D Increasing GLP-1 receptor stimulation by preventing GLP-1 degradation

Explanation

Metformin lowers glucose primarily by activating AMPK in the liver, which suppresses hepatic gluconeogenesis. It does not stimulate insulin secretion, so hypoglycemia is rare. Option B describes sulfonylureas, C describes acarbose, and D describes DPP-4 inhibitors. Harrison and Katzung both describe AMPK activation as the principal mechanism.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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