How metformin works
Metformin is a biguanide that works primarily by inhibiting hepatic gluconeogenesis — it reduces the amount of glucose the liver releases into the bloodstream. It also improves peripheral insulin sensitivity and decreases intestinal glucose absorption. Unlike sulphonylureas, it does not stimulate insulin secretion, so it does not cause hypoglycaemia on its own.
Standard dosing
Start at 500 mg once or twice daily with meals to minimise GI side effects. Increase slowly — typically by 500 mg per week — up to 2,000–2,500 mg/day in divided doses. Extended-release (XR) formulations are taken once daily with the evening meal and have fewer GI side effects.
Side effects
The main side effects are gastrointestinal: nausea, diarrhoea, abdominal discomfort. These affect up to 30% of patients at initiation and are dose-dependent. Most improve within 2–4 weeks. Starting at a low dose and increasing slowly is the most effective mitigation. Long-term use can reduce vitamin B12 absorption — annual B12 monitoring is recommended.
Lactic acidosis
Metformin carries a boxed warning for lactic acidosis, but this is rare (<1 in 100,000 patient-years) and almost entirely restricted to patients with severe renal impairment (eGFR <30), significant hepatic impairment, or acute illness causing dehydration. Metformin should be withheld before procedures using iodinated contrast dye.
Use in PCOS
Metformin is widely used off-label in polycystic ovary syndrome to improve insulin sensitivity, restore ovulation, and reduce hyperandrogenism. It is not licensed for this indication but is supported by strong evidence and international clinical guidelines.