The principal molecular mechanism by which metformin lowers blood glucose is:
- A Competitive inhibition of intestinal alpha-glucosidase enzymes
- B Stimulation of pancreatic beta cell K-ATP channel closure
- C Activation of AMP-activated protein kinase with suppression of hepatic gluconeogenesis ✓
- D Agonism at PPAR-gamma receptors in adipose tissue
Correct answer: C. Activation of AMP-activated protein kinase with suppression of hepatic gluconeogenesis
Explanation
Metformin enters hepatocytes via OCT1 and mildly inhibits mitochondrial complex I, raising the AMP to ATP ratio. This activates AMPK and suppresses gluconeogenic gene expression, reducing hepatic glucose output, the dominant effect behind its glucose lowering. It does not touch beta cell K-ATP channels, so it rarely causes hypoglycaemia as monotherapy. Alpha-glucosidase inhibition defines acarbose and PPAR-gamma agonism defines pioglitazone, making those options class-mismatched rather than merely incomplete.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.