Which of the following best describes the principal mechanism by which metformin lowers blood glucose?

• A Stimulation of pancreatic beta-cell insulin secretion via closure of ATP-sensitive potassium channels
• B Blockade of renal sodium-glucose cotransporter 2 with glycosuria
• C Competitive inhibition of intestinal alpha-glucosidase enzymes
• D Activation of AMP-activated protein kinase with inhibition of hepatic gluconeogenesis ✓

Explanation

Metformin acts mainly through AMPK activation, reducing hepatic gluconeogenesis and improving peripheral insulin sensitivity. It does not stimulate insulin secretion, so it rarely causes hypoglycaemia as monotherapy. Option A describes sulfonylureas such as glipizide, option C describes acarbose, and option B describes SGLT-2 inhibitors like empagliflozin. The distinguishing fact examined here is that metformin's effect requires some residual insulin but never causes insulin release itself.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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