Sulphonylureas Acarbose

Exogenous insulin or insulinotropic oral agents such as sulphonylureas are not suitable for improving insulin resistance. Non-insulinotropic hypoglycaemic medication such as biguanides and/or acarbose, however, is recommended if diet alone fails to achieve sufficient metabolic control. It is still controversial, however, whether the reduction of endogenous insulin also reduces the synthesis of islet amyloid polypeptide (IAPP) sufficiently to slow down the progression of NIDDM (Clark et al., 1987). 

There are three conditions for the clinical use of metformin as a glucose-lowering agent in patients with NIDDM (1) as a primary drug, (2) in combination with other oral hypoglycaemic agents such as sulphonylureas and acarbose, and (3) together with insulin after secondary sulphonylurea failure. 

Acarbose is used in diabetes in addition to other therapeutic regimes in connection with diet. Its clinical usefulness was demonstrated (Hanefeld et al., 1991) but its extent is a matter of controversy. However, a diet is preferable in Type-II diabetes. There are some studies which show the usefulness of its combination with sulphonylureas. Considerable individual variation is noted in the response to acarbose (Reaven et al., 1990). The use of acarbose in patients with NIDDM not well controlled by sulphonylureas appears to have significant clinical benefit (Raptis et al., 1982). One study suggests that it is not an effective substitute for sulphonylureas in non-obese Type-II diabetes uncontrolled by diet alone (Buchanan et al., 1988). 

For a review, see Sachse etal. (1982). Combining acarbose with sulphonylurea or metformin or insulin may lead to hypoglycaemia, although acarbose itself will not produce hypoglycaemia (doses have to be corrected). The effect of acarbose may be reduced by antacids, cholestyramine, pancreatic enzymes and adsorbants. Plasma levels of vitamin B6 increased, and vitamin A concentrations decreased with acarbose (Couet et al., 1989). 

The combination of acarbose and sulphonylureas is mainly used in patients with secondary sulphonylurea failure. Rosak (1990) reported a lowering of fasting blood glucose by 42 mg per 100 ml in diabetics treated with acarbose and sulphonylureas versus 14 mg per 100 ml with only sulphonylureas. Postprandial blood glucose was decreased by 57 mg per 100 ml, while sulphonylureas alone produced an increase of 4 mg per 100 ml in secondary sulphonylurea failure. 

The combination of sulphonylureas and acarbose (3 x 100 mg) versus sulphonylureas and phenformin (75 mg) was tested for 3 months by Pagano and Cavallo-Perin (1990), who could not find any significant difference between the two treatments as far as blood glucose, plasma insulin and HbA] were concerned. However, there was a 20% increase in plasma lactate in the biguanide group and no variation in the acarbose patients. 

In conclusion, the best indication for acarbose is in the early stages of NIDDM and in overweight diabetic patients who do not respond well to diet therapy. Acarbose can be used as monotherapy and also in association with sulphonylureas and insulin. It lowers postprandial and fasting blood glucose, decreases hypertriglyceridaemia and hyperinsulinaemia, and improves HbAj. It is therefore justified to expect also a beneficial effect of acarbose on the development of long-term diabetic complications. 

A report suggests that the hypocholesterolaemic effect of colestipol is unaffected in insulin-treated diabetics but it may be ineffective in those taking phenformin and sulphonylureas. Diabetic control was not affected. Colestyramine may enhance the effect of acarbose, and insulin levels may rebound if both drugs are stopped at the same time. There is evidence that the absorption of glipizide may be reduced by about 30% if it is taken at the same time as colestyramine, but tolbutamide does not appear to be affected. 

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