A patient with T2DM on metformin develops lactic acidosis. The sub-cellular mechanism responsible for this adverse effect is metformin's inhibition of:

• A Glucagon receptors on hepatocyte plasma membrane
• B Pyruvate carboxylase in the cytoplasm
• C Lactate dehydrogenase B in skeletal muscle
• D Mitochondrial complex I of the electron transport chain in hepatocytes ✓

Explanation

Metformin accumulates in mitochondria and inhibits complex I (NADH dehydrogenase) of the respiratory chain, reducing hepatic ATP production. This impairs the energy-dependent conversion of lactate to glucose (gluconeogenesis) in the liver, leading to lactate accumulation. Risk is highest in patients with renal impairment (metformin accumulates due to reduced renal clearance), hepatic disease or hypoxic states. Contraindicated in eGFR <30 mL/min.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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