A 45-year-old type 2 diabetic with eGFR of 35 mL/min/1.73m² is on metformin. What is the MOST serious risk that mandates discontinuation of metformin at this eGFR?

• A Hypoglycaemia due to impaired renal gluconeogenesis
• B Vitamin B12 deficiency worsening renal anaemia
• C Hyperkalemia due to inhibition of renal tubular transport
• D Lactic acidosis due to metformin accumulation ✓

Explanation

Metformin is renally cleared; when eGFR falls below 30 mL/min, metformin accumulates significantly and inhibits mitochondrial respiratory chain complex I, causing excess lactate production and reduced lactate clearance — resulting in potentially fatal lactic acidosis. Current guidelines recommend dose reduction when eGFR is 30-45 and complete discontinuation below 30. The risk is not hypoglycaemia since metformin does not stimulate insulin secretion.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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