Description

Metformin

Metformin has been the first-line oral medication for type 2 diabetes in most guidelines for decades, and the reasons go beyond just lowering blood sugar. Unlike insulin and many other diabetes drugs, metformin doesn’t cause weight gain — and in overweight patients it often produces modest weight reduction. It doesn’t cause hypoglycemia when used alone. And it has outcome data showing reduced cardiovascular events in overweight diabetics, not just glucose numbers. That combination is why it’s still the starting point.

Available in 500 mg and 850 mg tablets.

How it works

Metformin acts primarily on the liver: it reduces the amount of glucose the liver produces between meals (gluconeogenesis and glycogenolysis). It also increases muscle sensitivity to insulin, allowing cells to take up glucose more effectively, and modestly reduces intestinal glucose absorption. The result is lower fasting and post-meal blood glucose without the direct stimulation of insulin secretion that causes hypoglycemia.

Dosing

Starting low and increasing slowly is the standard approach — not because higher doses don’t work, but because the gastrointestinal side effects that cause many patients to stop are dose- and pace-dependent. A typical initiation is 500 mg once or twice daily with meals, increasing over several weeks. Maximum daily dose is 2000 mg (some extended-release formulations go to 2550 mg). Taking it with food reduces stomach upset significantly.

Lactic acidosis — rare but serious

The black box warning on metformin is for lactic acidosis — an accumulation of lactic acid in the blood that can be fatal. The word “rare” appears repeatedly in clinical literature, and it is rare. But the risk concentrates in specific situations: significant renal impairment (kidneys clear metformin, and accumulation drives lactic acid buildup), excessive alcohol intake, severe dehydration, hypoxic states, and hepatic dysfunction.

Alcohol combined with metformin specifically potentiates lactic acid accumulation. Even moderate alcohol consumption has been documented as sufficient to trigger metformin-associated lactic acidosis in the presence of even mild renal impairment. This is not a theoretical interaction.

Before any imaging procedure using iodinated contrast, metformin should be paused — contrast agents can cause acute kidney injury, which then traps metformin. Timing of the pause depends on the procedure and baseline kidney function; the radiologist and prescriber should coordinate.

Contraindications

Significant renal impairment — eGFR below 30 mL/min/1.73m² is a contraindication; between 30 and 45 requires dose adjustment and monitoring. Heart failure requiring pharmacological treatment. Conditions causing tissue hypoxia. Severe hepatic impairment.

Side effects

Gastrointestinal effects are by far the most common: diarrhea, nausea, abdominal cramps, flatulence. These affect a real proportion of patients and are the most frequent reason people stop taking it. Starting at a low dose and titrating slowly reduces but doesn’t eliminate this. Taking it with meals helps. The effects typically diminish over several weeks as the body adjusts.

With long-term use — years rather than months — metformin impairs absorption of vitamin B12 and, to a lesser extent, folate. B12 deficiency is clinically significant because it causes peripheral neuropathy and cognitive changes that can be mistaken for diabetic complications. Periodic monitoring of B12 levels and supplementation if needed is standard practice for patients on metformin for several years.

Beyond diabetes

Metformin is used off-label for polycystic ovary syndrome — where insulin resistance and elevated androgens are central to the condition — and has shown benefit for menstrual regularity and metabolic parameters in PCOS. It’s also used for prediabetes, where evidence supports its role in reducing progression to type 2 diabetes, particularly in high-risk individuals.