Background

In the United States in 1990, there were around 23 million prescriptions issued for oral hypoglycaemic drugs. These were almost entirely for sulphonylureas. A decade later, the number of prescriptions had risen to over 90 million. While the variety of drugs had increased, sulphonylureas were still the most commonly prescribed drugs for type 2 diabetes, and are the initial treatment of choice for patients who are not overweight (Figure 19.1). The drugs bind to a complex of the sulphonylurea receptor (SUR) and an ATP-sensitive potassium channel (kir6.2) on the surface of the pancreatic beta cell. Binding of the drug leads to closure of the potassium channels, as a result of which potassium efflux is inhibited, the cell becomes depolarized, and calcium channels in the endoplasmic reticu-lum open. Contraction of microtubules in response to this leads to exocytosis of insulin.1 The available sulphonylurea drugs include gliclazide, glibenclamide and glimepiride. All have similar potency in decreasing glycosylated haemoglobin (HbA1c) by between 1.0% and 1.5% in the short to medium term. The older sulphonylureas, tolbutamide (short-acting) and chlorpopamide (long-acting), are now rarely used. This group of drugs is generally well tolerated, sometimes causing mild gastrointestinal upset and occasionally causing allergic reactions. The most common side effects are weight gain and hypogly-caemia. One can expect a patient starting sulphonylureas to gain 2-5 kg in the first few months. Hypoglycaemia is generally mild but may affect up to 2% of treated patients per year. Glimepiride and modified-release gliclazide are convenient preparations as they can be taken once daily.

Review diet

Review diet

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