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Drug Reference

metformin

Biguanide· Brands: Glucophage, Metfogamma, Riomet, Fortamet, GlumetzaPO

Mechanism of action
Metformin reduces hepatic glucose production, improves insulin sensitivity in peripheral tissues, and decreases intestinal glucose absorption. It does not stimulate insulin secretion, so hypoglycaemia is uncommon when used alone.
Pharmacokinetics
Metformin is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring about 2 to 3 hours after oral administration. It is not significantly bound to plasma proteins and is not metabolised. It is excreted unchanged in the urine, with a half-life of approximately 6 hours. Renal impairment can lead to accumulation.
Indications & dosing

Type 2 diabetes mellitus

Take with meals to reduce gastrointestinal upset. Titrate slowly to minimise side effects.

  • adult · PO: 500–850 mg once to twice daily · Take with meals to reduce gastrointestinal upset. Titrate slowly to minimise side effects.

Type 2 diabetes mellitus in children

For children aged 10 years and older. Use requires specialist guidance.

  • pediatric · PO: 500 mg twice daily · For children aged 10 years and older. Use requires specialist guidance.

Polycystic ovary syndromeoff-label

Off-label use for insulin resistance in PCOS. May improve ovulation and menstrual regularity.

  • adult · PO: 500–850 mg once to twice daily · Off-label use for insulin resistance in PCOS. May improve ovulation and menstrual regularity.
Contraindications & precautions
  • Severe renal impairment (eGFR <30 mL/min/1.73 m2) · Metformin accumulates and increases risk of lactic acidosis.
  • Acute conditions that cause tissue hypoxia (e.g., decompensated heart failure, respiratory failure, recent MI, shock) · Risk of lactic acidosis is increased.
  • Metabolic acidosis, including diabetic ketoacidosis · Metformin is contraindicated in any form of metabolic acidosis.
  • Hepatic impairment · Risk of lactic acidosis is increased due to impaired lactate metabolism.
  • Alcohol abuse or dependence · Alcohol increases the risk of lactic acidosis; advise caution or abstinence.
  • Monitor renal function at baseline and at least annually; more frequently in those with renal impairment or risk factors.
  • Withhold metformin before and after administration of iodinated contrast media if eGFR is low or at risk of contrast-induced nephropathy.
  • Avoid alcohol excess to reduce the risk of lactic acidosis.
  • Use with caution in moderate renal impairment (eGFR 30-45 mL/min/1.73 m2); consider dose reduction or withholding if conditions increase lactic acidosis risk.
  • Temporarily withdraw before surgery under general anaesthesia, especially if renal function may be affected.
  • Monitor vitamin B12 levels in long-term therapy, especially in those with neuropathies or risk factors for deficiency.
Adverse effects
  • Diarrhoea
  • Nausea
  • Vomiting
  • Abdominal pain
  • Loss of appetite
  • Metallic taste
  • Lactic acidosisserious
  • Vitamin B12 deficiency (long-term use)
Interactions
  • prednisolonemoderateMonitor blood glucose regularly when prednisolone is started, stopped, or the dose is changed. Consider adjusting the metformin dose, adding other antihyperglycaemic agents, or using a non-steroidal alternative if appropriate for the underlying condition.
Renal & hepatic adjustment
  • eGFR 45–60: Consider reducing dose if already on therapy; monitor renal function frequently.
  • eGFR 30–44: Use with caution. If already on treatment, reduce dose (max 1000 mg/day) and monitor closely.
  • eGFR 0–29: Contraindicated. Stop metformin. (avoid)
  • Hepatic impairment (mild): MILD hepatic impairment: Avoid. Metformin is contraindicated in hepatic insufficiency due to the risk of lactic acidosis.
  • Hepatic impairment (moderate): Use with caution; monitor liver function.
  • Hepatic impairment (severe): Avoid. Metformin is contraindicated in severe hepatic impairment. (avoid)
Monitoring, pregnancy & toxicity
  • eGFR · At least annually; more frequently if eGFR is 30-60 mL/min or risk of deterioration.
  • HbA1c · Every 3-6 months.
  • Serum vitamin B12 · If symptoms of deficiency or long-term use.
  • Lactate · If signs of lactic acidosis.
  • Pregnancy: Metformin can be used in pregnancy for the treatment of type 2 diabetes or gestational diabetes, but insulin is often preferred. It crosses the placenta; limited data suggest no increased risk of congenital anomalies. If used, monitor carefully.
  • Toxicity: Lactic acidosis (rare but serious): symptoms include nausea, vomiting, abdominal pain, rapid breathing, lethargy, and hypotension. · Stop metformin, hospitalise urgently. Consider haemodialysis. Give supportive care. Check blood lactate and renal function.
  • Toxicity: Hypoglycaemia (unlikely unless combined with other agents or excessive alcohol) · Give oral glucose if conscious; treat with intravenous dextrose if severe.
  • Toxicity: GI disturbances (diarrhoea, nausea) in overdose · Supportive care.
Clinical notes
Metformin is first-line for type 2 diabetes. The most common adverse effects are gastrointestinal, including diarrhoea, nausea, and abdominal discomfort. Lactic acidosis is rare but serious, with risk increased by renal impairment, dehydration, and iodinated contrast. Monitoring of renal function is essential. It should be stopped before administration of iodinated contrast media. Long-term use may cause vitamin B12 deficiency.

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BNF; local formulary