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Other sulphonylureas include tolbutamide, gliquidone, glibornuride, tolazamide.

Other sulphonylureas include tolbutamide, gliquidone, glibornuride, tolazamide.

Sulphonamides, as expected, potentiate sulphonylureas by direct action and by displacement from plasma proteins.

Gliclazide is a commonly used second generation sulphonylurea. If more than 80 mg is prescribed, the drug should be taken twice daily before meals.

Glimepiride is designed to be used once daily and to provoke less hypoglycaemia than glibenclamide.

Repaglinide is a very short-acting oral hypogly-caemic agent whose action, like the sulphonylureas, is mediated through blockade of ATP-dependent potassium channels. It affects only postprandial insulin profiles, and should in theory reduce risk of hypoglycaemia.

Biguanides (see also Table 35.1)

Metformin (t\ 5 h) is taken with or after meals. Its chief use is in the obese patient with Type 2 diabetes either alone or in combination with a sulphonylurea. It has a mild anorexic effect which helps to reduce weight in the obese. The action of metformin is terminated by excretion by the kidney and it should not be used in the presence of renal impairment.

Minor adverse gut reactions are common, including nausea, diarrhoea, and a metallic taste in the mouth. These symptoms are usually transient or subside after reduction of dose. Heavy prolonged use can cause vitamin B12 deficiency due to malabsorption. With a biguanide, ketonuria may occur in the presence of normal blood sugar. This is not generally severe and responds to reduction of dose. More serious, but rare, is lactic acidosis, which occurs in 0.03 cases per 1000 patient years. When this condition does occur, it is usually against the background of a serious underlying medical state such as renal impairment, liver failure or cardiogenic or septic shock. Lactic acidosis is treated with large (i.v.) doses of isotonic sodium bicarbonate.

Thiazolidinediones (see also Table 35.1)

Pioglitazone, is indicated once daily in patients not controlled by metformin alone. It is contraindicated by cardiac or hepatic failure. Weight gain and oedema are the main adverse effects.

Rosiglitazone is similar and is administered once or twice daily.

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