Biguanide Pregnancy: A large amount of data on pregnant women (more than 1000 exposed outcomes) indicates no increased risk of congenital abnormalities or feto/neonatal toxicity after exposure in the periconceptional phase and/or during pregnancy; if clinically needed, metformin can be considered during pregnancy as an addition or alternative to insulin. Metformin crosses the placenta at levels that can be as high as maternal concentrations. Breast-feeding is not recommended during metformin treatment as only limited data are available.

Metformin hydrochloride

Brand names: Glucophage, Metformin SR

A biguanide oral antidiabetic and the recommended first-line drug treatment for type 2 diabetes, also used in selected patients for prediabetes and polycystic ovary syndrome.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 500 mg or 850 mg metformin hydrochloride

Route: Oral

Frequency: 2 or 3 times daily, given during or after meals

Max: 3 g metformin hydrochloride daily, taken as 3 divided doses

UK SPC section 4.2, adults with normal renal function (GFR at least 90 mL/min), monotherapy or combination with other oral antidiabetic agents. Doses in this record refer to the metformin hydrochloride salt. After 10 to 15 days the dose should be adjusted on the basis of blood glucose measurements; a slow increase of dose may improve gastrointestinal tolerability. If transferring from another oral antidiabetic agent, discontinue the other agent and initiate metformin at the dose above. Combination with insulin: metformin hydrochloride is given at the usual starting dose of 500 mg or 850 mg 2 or 3 times daily while the insulin dose is adjusted on the basis of blood glucose measurements. Elderly: adjust the dose based on renal function, with regular assessment of renal function. Paediatric population: metformin hydrochloride can be used in children from 10 years of age and adolescents - usual starting dose 500 mg or 850 mg once daily during or after meals, adjusted after 10 to 15 days on the basis of blood glucose, to a maximum recommended dose of 2 g daily taken as 2 or 3 divided doses; verify paediatric dosing against a children's formulary. Discontinue prior to or at the time of intravascular administration of iodinated contrast agents (risk of contrast-induced nephropathy leading to metformin accumulation and lactic acidosis).

Dose adjustments

Renal

Assess GFR before initiation and at least annually thereafter (every 3 to 6 months in patients at increased risk of progression and in the elderly). Total maximum daily dose, divided into 2 to 3 daily doses: GFR 60-89 mL/min - 3000 mg (dose reduction may be considered in relation to declining renal function); GFR 45-59 mL/min - 2000 mg (review factors that may increase the risk of lactic acidosis before initiation; the starting dose is at most half of the maximum dose); GFR 30-44 mL/min - 1000 mg; GFR below 30 mL/min - metformin is contraindicated. Temporarily discontinue in the presence of conditions that alter renal function.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to metformin or to any of the excipients
Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis)
Diabetic pre-coma
Severe renal failure (GFR below 30 mL/min)
Acute conditions with the potential to alter renal function such as dehydration, severe infection or shock
Disease which may cause tissue hypoxia (especially acute disease or worsening of chronic disease) such as decompensated heart failure, respiratory failure or recent myocardial infarction
Hepatic insufficiency, acute alcohol intoxication, alcoholism

Side effects

Very common: gastrointestinal disorders such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite, most frequent at initiation and usually resolving spontaneously
Common: vitamin B12 decrease/deficiency
Common: taste disturbance
Very rare: lactic acidosis
Very rare: liver function test abnormalities or hepatitis, resolving on discontinuation
Very rare: skin reactions such as erythema, pruritus, urticaria

Interactions

Medicinal products that can acutely impair renal function (antihypertensives, diuretics, NSAIDs): initiate with caution in metformin-treated patients (UK SPC section 4.4)
Iodinated contrast agents: intravascular administration may cause contrast-induced nephropathy, metformin accumulation and increased risk of lactic acidosis - metformin should be discontinued prior to or at the time of the imaging procedure (UK SPC section 4.4)
Alcohol: potentiates the effect of metformin on lactate metabolism; excessive alcohol intake is a risk factor for lactic acidosis
Carbonic anhydrase inhibitors (topiramate, zonisamide, acetazolamide, dichlorphenamide): decrease serum bicarbonate and may increase the risk of lactic acidosis - consider more frequent monitoring (US labelling)
Drugs that reduce metformin clearance (OCT2/MATE inhibitors such as ranolazine, vandetanib, dolutegravir, cimetidine): increased systemic metformin exposure and risk of lactic acidosis (US labelling)
Insulin or insulin secretagogues: increased risk of hypoglycaemia - a lower dose of insulin or secretagogue may be required (US labelling)

Clinical monograph

How it works

It lowers blood glucose chiefly by reducing hepatic gluconeogenesis and by increasing peripheral insulin sensitivity, without stimulating insulin secretion, so it does not itself cause hypoglycaemia.

Prescribing in practice

The rare but serious risk is lactic acidosis, so it is contraindicated or must be withheld in significant renal impairment, tissue hypoxia, acute dehydrating illness, and around iodinated contrast and major surgery.
Gastrointestinal upset is common; introducing it gradually with food or using a modified-release preparation improves tolerability.
Long-term use can reduce vitamin B12 absorption, which should be considered in patients with anaemia or neuropathy.

Monitoring

Monitor HbA1c and renal function (eGFR), with periodic vitamin B12 checks during prolonged therapy.

Counselling the patient

Take with or just after meals to reduce nausea and diarrhoea.
Stop temporarily and seek advice if you become acutely unwell with vomiting, diarrhoea or dehydration, or before a scan using contrast dye.
It does not usually cause low blood sugar on its own, but this can occur if combined with other diabetes medicines.

Evidence & guidelines

Metformin is the established first-line agent in NICE type 2 diabetes guidance, with long-term cardiovascular benefit demonstrated in the UKPDS.

Reference: NICE NG28; MHRA Drug Safety Update; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Drugs

Metformin · Biguanide

Pathways

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