๐ Tolbutamide is a short-acting sulfonylurea used in the management of type 2 diabetes mellitus (T2DM).
It lowers blood glucose by stimulating pancreatic insulin secretion but carries a risk of hypoglycaemia, especially in elderly or renally impaired patients.
Its short half-life makes it safer than longer-acting agents (e.g. glibenclamide) in older adults.
๐ About
- Always check the BNF entry for latest dosing, interactions, and cautions.
- First-generation sulfonylurea โ shorter acting than chlorpropamide or glibenclamide.
- Now largely replaced by newer agents (e.g. gliclazide) but still useful for short-term glycaemic control or diagnostic testing.
โ๏ธ Mode of Action
- Stimulates insulin release by binding to the sulfonylurea receptor (SUR1) on pancreatic ฮฒ-cells โ closes KATP channels โ depolarisation โ calcium influx โ insulin exocytosis.
- Also reduces hepatic gluconeogenesis and increases peripheral glucose uptake.
- Requires functioning ฮฒ-cells โ not effective in type 1 diabetes.
๐ Indications
- Type 2 diabetes mellitus inadequately controlled by diet and lifestyle measures alone.
- Sometimes used in diagnostic testing for insulin secretion (in endocrinology settings).
๐ Dose
- T2DM: 0.5โ1.5 g daily in divided doses with meals (max 2 g/day).
- Start low and titrate gradually based on blood glucose response.
- Avoid skipping meals โ risk of hypoglycaemia.
๐ Interactions
- Increased hypoglycaemia risk with: chloramphenicol, sulfonamides, co-trimoxazole, warfarin, fibrates, NSAIDs.
- Reduced effect with corticosteroids, thiazides, or phenytoin.
- Alcohol may enhance hypoglycaemia and cause flushing reaction.
โ ๏ธ Cautions
- Use cautiously in renal or hepatic impairment โ slower clearance increases toxicity risk.
- In obese patients, sulfonylureas may promote weight gain โ combine or switch to metformin for better metabolic outcomes.
- Stop and consider variable-rate insulin infusion (VRIII) during acute illness or perioperatively.
๐ซ Contraindications
- Type 1 diabetes, diabetic ketoacidosis (DKA).
- Severe hepatic or renal impairment.
- Known hypersensitivity to sulfonylureas or sulfonamides.
๐ฅ Adverse Effects
- ๐ง Hypoglycaemia โ main risk; can cause confusion, sweating, and collapse.
- โ๏ธ Weight gain due to increased insulin levels.
- GI upset, nausea, rash, or photosensitivity.
- Rare: hepatotoxicity, cholestatic jaundice, and blood dyscrasias (e.g. agranulocytosis).
๐ง Teaching Note
Tolbutamide illustrates the core mechanism of sulfonylureas: KATP channel blockade โ insulin release.
Its short half-life (4โ8 hours) makes it a safer prototype for elderly or renally compromised patients.
Always educate patients on recognising and treating hypoglycaemia โ a key safety issue for all insulin secretagogues.
๐ References
- BNF: Tolbutamide
- NICE NG17: Type 2 Diabetes in Adults (2024)
- UKCPA Handbook of Perioperative Medicines
