Metformin is contraindicated when eGFR falls below 30 mL/min/1.73m2 primarily because renal impairment increases the risk of which potentially fatal complication?

• A Hypoglycaemic coma from reduced renal gluconeogenesis
• B Acute tubular necrosis from direct nephrotoxicity of metformin
• C Lactic acidosis due to metformin accumulation inhibiting mitochondrial complex I ✓
• D Vitamin B12 deficiency-induced peripheral neuropathy

Explanation

Metformin accumulates in renal impairment because it is renally excreted unchanged. High intracellular metformin concentrations inhibit mitochondrial complex I (NADH dehydrogenase), shifting hepatic metabolism toward anaerobic glycolysis and causing lactic acidosis — a rare but mortality-carrying complication (mortality ~50%). Metformin does not itself cause hypoglycaemia as it does not stimulate insulin secretion. B12 malabsorption (from ileal receptor competition) is a real but less acute concern.

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

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Written and medically reviewed by the StethoPrep medical team.