A patient with T2DM and CKD stage 3b (eGFR 35 mL/min/1.73m²) is on metformin. Metformin should be dose-reduced or discontinued at this eGFR because:

• A Metformin is nephrotoxic and worsens CKD at reduced eGFR
• B Reduced renal excretion causes metformin accumulation, increasing lactic acidosis risk via mitochondrial complex I inhibition ✓
• C Metformin activates AMPK less effectively in CKD, reducing its glucose-lowering effect
• D Metformin causes hyperkalemia at eGFR below 45 mL/min

Explanation

Metformin is entirely renally excreted unchanged. In CKD, accumulation of metformin inhibits mitochondrial complex I of the electron transport chain in hepatocytes, impairing oxidative phosphorylation and promoting anaerobic glycolysis, leading to lactic acidosis. Current guidelines allow reduced dosing at eGFR 30–45 mL/min and recommend stopping below eGFR 30 mL/min. Metformin itself is not nephrotoxic; lactic acidosis risk, not renal damage, is the concern.

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

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Written and medically reviewed by the StethoPrep medical team.