First-generation sulfonylurea (short-acting) Pregnancy: Oral hypoglycaemics are not indicated for use by the pregnant diabetic as they will not provide good control of plasma glucose levels in patients who cannot be controlled by diet alone — insulin should be used to control gestational diabetes if dietary control is not sufficient. Tolbutamide should not be used during the first trimester of pregnancy; there is some evidence of harmful effects in animals and isolated reports suggesting a hazard in human pregnancy, and placental transfer may result in prolonged hypoglycaemia in the neonate. If tolbutamide is to be used in pregnancy, treatment should be changed to insulin at least 4 days prior to delivery. Breast-feeding: tolbutamide has been detected in breast milk in small quantities with a theoretical risk of neonatal hypoglycaemia — breast-feeding is best avoided (and breast feeding women are listed as a contraindication in section 4.3).

Tolbutamide

Tolbutamide is a short-acting first-generation sulfonylurea formerly used to lower blood glucose in type 2 diabetes mellitus. Its relatively short duration of action made it a comparatively lower-risk choice for hypoglycaemia among older sulfonylureas.

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: Treatment of previously untreated diabetes: stabilisation can be achieved commencing with 2 tablets (1 g) daily, adjusting in the light of the patient's individual response. The average daily dose is 1-3 tablets (0.5-1.5 g).

Route: Oral administration

Frequency: As a single dose with, or immediately after, the first main meal of the day, or as a divided dose for optimum control of blood sugar

Max: In general, patients who do not respond to 4 tablets (2 g) do not respond to higher doses

Source product is Tolbutamide Tablets BP 500 mg, so the SPC's 'tablets' are 500 mg each. CHANGE OVER FROM OTHER ORAL HYPOGLYCAEMICS: it is possible to freely interchange hypoglycaemic agents (including chlorpropamide) without a break in treatment; stabilisation can initially be achieved with 2 tablets (1 g) daily, followed by a maintenance dose depending on response. COMBINATION WITH BIGUANIDES: if adequate control is not achieved with diet and 4 tablets (2 g) of tolbutamide daily, it can often be achieved by combined administration with a biguanide derivative. CHANGE OVER FROM INSULIN: some patients with non-insulin dependent diabetes already taking insulin may be changed to tolbutamide — low insulin doses (less than 20 units) can be replaced immediately, while with higher doses a gradual change is advisable, giving insulin and tolbutamide concurrently and gradually reducing the insulin dose. ELDERLY: tolbutamide is particularly suitable for elderly patients as the risk of hypoglycaemia is lower than with other sulfonylureas; however, treatment should be initiated at a lower dose. Elderly patients are especially sensitive to sulfonylurea-induced hypoglycaemia, with insidious onset and prolonged impaired performance. Debilitated or aged patients, or those who have difficulty metabolising tolbutamide, may be more liable to hypoglycaemia. Should not be used as a substitute for dietary treatment in obese patients. If fever or a sore throat occurs, perform a white cell count and repeat after five days, as blood abnormalities may develop slowly; perform a platelet count if thrombocytopenia is suspected. Caution in G6PD deficiency (sulfonylureas can lead to haemolytic anaemia) — a non-sulfonylurea alternative should be considered. PAEDIATRIC POPULATION: 'There is insufficient data on the efficacy and safety of tolbutamide in children and adolescents and therefore its use in this age group is not recommended.'

Dose adjustments

Renal

Contraindicated in patients with serious impairment of renal function. Patients with mild to moderate renal impairment should start with lower doses and have careful monitoring of blood glucose levels.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substance(s) or to any of the excipients
Patients who have, or have ever had, diabetic ketoacidosis
Patients with insulin-dependent diabetes mellitus
Patients with serious impairment of renal, hepatic, adrenocorticoid or thyroid function
Patients in circumstances of unusual stress (e.g. surgical operations or during pregnancy) when dietary treatment and insulin are essential
Patients with porphyria
Women who are breast feeding

Side effects

Hypoglycaemia and hypoglycaemic symptoms — reported when tolbutamide has been administered without due regard to the patient's dietary habits
Gastrointestinal: nausea, vomiting, diarrhoea, anorexia, increased appetite, weight gain and constipation
Blood disorders (rare): leukopenia, thrombocytopenia, agranulocytosis, pancytopenia, haemolytic anaemia and aplastic anaemia
Hypersensitivity reactions, usually within 6 to 8 weeks of starting treatment; allergic skin reactions which rarely progress to erythema multiforme, exfoliative dermatitis and fever; photosensitivity
Hepatobiliary: disturbances in liver function and cholestatic jaundice
Nervous system: paraesthesia and headache; intolerance to alcohol. Ear: tinnitus

Interactions

Hypoglycaemic effect ENHANCED by: coumarin anticoagulants (e.g. dicoumarol and warfarin), MAOIs, beta-adrenergic blocking agents, sulphonamides, phenylbutazone, chloramphenicol, cyclophosphamide and salicylates
Hypoglycaemic effect DIMINISHED by: adrenaline, lithium, rifampicin, corticosteroids, oral contraceptives or thiazide diuretics
Should NOT be co-administered with sulfafurazole or coumarins — severe hypoglycaemic reactions have occurred
Alcohol should be avoided since it may cause a disulfiram-like reaction

Clinical monograph

How it works

It binds to the sulfonylurea receptor on pancreatic beta cells, closing ATP-sensitive potassium channels to cause membrane depolarisation and stimulate endogenous insulin secretion, and therefore requires functioning beta cells to be effective.

Prescribing in practice

Like all sulfonylureas it can cause hypoglycaemia, which though generally shorter-lived than with longer-acting agents can still be serious, particularly in the elderly or those with renal or hepatic impairment.
It is ineffective in type 1 diabetes and should not be used in diabetic ketoacidosis.
Weight gain can occur, and caution is needed in hepatic and renal impairment.

Monitoring

Monitor blood glucose and HbA1c for glycaemic control and remain alert for symptoms of hypoglycaemia, especially in the elderly and those with renal or hepatic impairment.

Counselling the patient

Take your dose with or shortly before a meal and do not skip meals.
Learn to recognise and treat low blood sugar, such as sweating, shakiness, or confusion.
Report episodes of low blood sugar to your clinician.

Evidence & guidelines

Its glucose-lowering action is well established through long-standing historical clinical use, though newer agents are generally now preferred.

Reference: NICE NG28; 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.

Calculators

Pathways