Metformin / Glucophage
Metformin is the only oral diabetes drug that doesn't cause hypoglycemia when used alone — but it carries a rare, lethal risk most students underestimate.
Core Concept
Metformin is first-line therapy for type 2 diabetes. It works primarily by decreasing hepatic glucose production and improving insulin sensitivity in peripheral tissues — it does NOT stimulate insulin secretion. Because it doesn't push insulin release, it rarely causes hypoglycemia as monotherapy. The most dangerous adverse effect is lactic acidosis, a rare but life-threatening complication. Risk increases sharply when metformin accumulates — most commonly due to renal impairment. Serum creatinine and eGFR must be monitored: metformin is contraindicated when eGFR falls below 30 mL/min and requires dose reduction below 45 mL/min. It must be held before any procedure using iodinated contrast dye and for 48 hours after, with reinstatement only after renal function is confirmed stable. GI side effects (nausea, diarrhea, metallic taste) are the most common reason patients stop taking it; starting at a low dose and taking it with food reduces these effects. Long-term use depletes vitamin B12, so periodic B12 levels should be monitored. Metformin is weight-neutral or promotes modest weight loss — a distinct advantage over many other oral agents.
Watch Out For
Don't confuse metformin's mechanism (decreases hepatic glucose output) with sulfonylureas (stimulate pancreatic insulin secretion) — this difference explains why metformin alone doesn't cause hypoglycemia. Students often think lactic acidosis is common; it's rare but has a high mortality, so the focus is prevention through renal monitoring. Holding metformin for contrast dye is about protecting the kidneys from accumulation, not a direct drug-dye interaction.
Clinical Pearl
Metallic taste, GI upset, and no hypoglycemia — that's metformin. But if your patient's eGFR is dropping, that drug becomes a ticking clock for lactic acidosis.
Test Your Knowledge
3 quick questions — see how well you understood Metformin / Glucophage