Metformin
Metformin
Generic Name
Metformin
Mechanism
Decreases hepatic gluconeogenesis, improves insulin‑mediated glucose uptake in peripheral tissues (primarily skeletal muscle), and modestly inhibits intestinal glucose absorption.
Pharmacokinetics
- Oral absorption: ~50 % bioavailability; peak plasma 1–2 h.
- Renally eliminated unchanged; half‑life ≈ 4–8 h (longer in CKD).
- No hepatic metabolism → no active metabolites.
Clinical Pearls
- Cimetidine, diuretics (e.g., furosemide), and ions (Na⁺, K⁺, Ca²⁺, Mg²⁺) → ↑ plasma metformin.
- Contrast agents (especially iodinated) → ↑ risk of lactic acidosis.
- Alcohol or drugs that decrease renal perfusion (ACEi, ARB, NSAIDs) → ↑ metformin levels.
Clinical Notes
Metformin (Glucophage) is a biguanide and first-line oral agent for type 2 diabetes mellitus.
| Indication | Type 2 diabetes mellitus (first-line therapy); polycystic ovary syndrome (off-label); prediabetes (off-label for prevention) |
|---|---|
| Mechanism of Action | Decreases hepatic glucose production, decreases intestinal glucose absorption, improves insulin sensitivity by increasing peripheral glucose uptake and utilization; does not cause hypoglycemia alone |
| Pharmacokinetics | 50-60% oral bioavailability (decreased with food); not protein bound; not metabolized; renal excretion unchanged; half-life 6 hours; steady state 24-48 hours |
| Dosing | IR: Start 500 mg PO BID (or 850 mg daily) with meals, max 2550 mg/day. ER: Start 500-1000 mg daily with evening meal, max 2000-2500 mg/day. Titrate gradually to reduce GI effects |
| Contraindications | eGFR <30 mL/min/1.73m², metabolic acidosis, diabetic ketoacidosis; avoid initiating if eGFR 30-45 |
| Adverse Effects | GI (diarrhea, nausea, metallic taste – usually transient), vitamin B12 deficiency (long-term), lactic acidosis (rare but serious, especially with renal impairment) |
| Drug Interactions | Iodinated contrast – hold before and 48 hours after (AKI risk); carbonic anhydrase inhibitors increase lactic acidosis risk; alcohol increases lactic acidosis risk |
| Monitoring | A1c every 3-6 months; renal function at least annually (more frequently if eGFR <60); B12 levels periodically (especially if anemia/neuropathy); lactic acid if symptomatic |
| Other Considerations | Weight neutral or slight loss; cardiovascular benefit suggested; BLACK BOX: lactic acidosis risk; hold 48h around iodinated contrast; reduce dose if eGFR 30-45 |
| Reference | UpToDate, Lexicomp, ADA Standards of Care, Glucophage prescribing information |
Quick-reference tip: Metformin – first-line for T2DM; avoid if eGFR <30; hold 48h around contrast; BLACK BOX for lactic acidosis; check B12 periodically.
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