## Cimetidine–Metformin Interaction ### Mechanism of Interaction **Key Point:** Cimetidine inhibits renal tubular secretion of metformin (via OCT2 transporter inhibition), NOT hepatic metabolism. This reduces metformin clearance and increases plasma concentration. ### Why Glucuronidation Induction Is Wrong **High-Yield:** Metformin is NOT metabolized by hepatic glucuronidation. It is eliminated unchanged by renal filtration and active tubular secretion. Cimetidine blocks the tubular secretion step, not metabolism. **Clinical Pearl:** Cimetidine is a potent inhibitor of multiple renal organic cation transporters (OCT1, OCT2, OCT3). Metformin is a substrate for OCT2 in the proximal tubule, so cimetidine impairs its active secretion and increases systemic exposure. ### Clinical Consequences | Consequence | Details | |-------------|----------| | **Increased metformin levels** | Plasma concentration rises by 30–50% | | **Risk of lactic acidosis** | Especially in patients with renal impairment (eGFR < 60 mL/min) | | **Management** | Monitor renal function; consider alternative H₂-blocker (ranitidine, famotidine — weaker inhibitors); reduce metformin dose if necessary | ### Why Each Option Is Correct (Except the Answer) 1. **Renal tubular secretion inhibition** ✓ — Cimetidine blocks OCT2-mediated secretion in the proximal tubule 2. **Increased plasma concentration + lactic acidosis risk** ✓ — Direct consequence of reduced clearance 3. **Hepatic glucuronidation induction** ✗ — Metformin is NOT glucuronidated; this mechanism does not apply 4. **Monitoring and dose adjustment** ✓ — Standard clinical practice for this interaction [cite:KD Tripathi 8e Ch 12]
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