Metformin
Brand names: Glucophage, Fortamet, Glumetza
Class: 🩸 Antidiabetics
The AANP exam tests metformin as the first drug for nearly every patient with type 2 diabetes — and as the drug whose only real contraindication candidates miss is impaired renal function. It activates AMPK, decreases hepatic gluconeogenesis, improves peripheral insulin sensitivity, and is weight-neutral with the lowest hypoglycemia risk among glucose-lowering agents. Indications also include prediabetes (especially BMI ≥35 or age <60) and PCOS off-label. Hold metformin for iodinated contrast, eGFR <30, or acute illness — lactic acidosis is the rare but feared harm. GI side effects (diarrhea, cramping, metallic taste) drive most discontinuations; titrate slowly and use the extended-release formulation. Long-term use causes B12 deficiency — recheck periodically.
✅ Indications
First-line for type 2 diabetes, prediabetes, PCOS (off-label), weight maintenance in diabetes.
⚙️ Mechanism of Action
Biguanide — ↓ hepatic gluconeogenesis, ↑ peripheral insulin sensitivity.
📏 Dosing
500 mg BID with meals, titrate to 1000 mg BID (max 2000–2550 mg/day).
🚫 Contraindications
eGFR <30, acute/chronic metabolic acidosis, severe hepatic impairment, alcohol abuse, acute illness with hypoperfusion risk.
⚠️ Adverse Effects
GI (diarrhea, cramping — often self-limited), metallic taste, B12 deficiency (long-term), LACTIC ACIDOSIS (rare but serious), NO hypoglycemia as monotherapy.
🔬 Monitoring
Annual B12 (long-term use), creatinine/eGFR annually. Hold before contrast imaging if eGFR <30.
💎 Board Pearls
- 🏆 First-line for T2DM, period.
- ⏸️ HOLD before IV contrast + major surgery (lactic acidosis risk).
- 🩸 Does NOT cause hypoglycemia alone → #1 choice in monotherapy.
- 🍎 Long-term → B12 deficiency (peripheral neuropathy) — check annually.
- 📉 eGFR <30 = CONTRAINDICATED; 30–45 = reduce dose.
Practice Questions
Which of the following antidiabetic medications, when used as monotherapy, carries essentially no intrinsic risk of hypoglycemia?
Related Drugs in This Class
- Glipizide — Glucotrol
- Empagliflozin — Jardiance
- Semaglutide — Ozempic (injectable), Wegovy (weight), Rybelsus (oral)
- Insulin Glargine — Lantus, Basaglar, Toujeo
- Insulin Lispro — Humalog
Sources
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