Biguanides NIDDM

Three classes of oral therapeutic agent are available for treating patients with diabetes mellitiis (NIDDM) the arylsulfonylureas (known simply as sulfonylureas), biguanides, and a-glycosidase inhibitors. Since 1977, only the sulfonylureas have been approved for use in the United States, although the other classes are used elsewhere. 

This review will concentrate on new agents or new data on older agents reported in the past 5 years, and is confined to compounds with reported hypoglycaemic activity in man and/or animal models of IDDM or NIDDM. The patent literature has been recently reviewed [6] and will not be covered here. Established agents (sulphonylureas, biguanides) have been the subject of recent reviews and the reader is referred to those [4, 7-12]. 

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). 

In conclusion, it can be stated, that biguanides, preferably metformin, have been shown in innumerable clinical trials to be highly effective as antihyper-glycaemic drugs. Together with acarbose, they may be the first-choice drug for the treatment of obese hyperinsulinaemic, insulin resistant Type-II diabetics with dietary failure. They help to correct most of the unwanted aspects of the metabolic syndrome, which is felt to contribute most to the high mortality rate of NIDDM patients with heart disease. 

The therapeutic effects of acarbose and biguanides have been compared in Type-II diabetics (Pagano and Cavallo-Perin, 1990) and found to be nearly equally effective. The same was true in studies (by Schwedes et al. (1982), who compared acarbose and metformin in poorly controlled NIDDM, while Schoffling et al. (1982) reported that acarbose was even more effective than metformin. Drost et al. (1982) concluded from their studies, however, that there was no basic difference between the hypoglycaemic effects of acarbose and metformin. Petersen (1982) tested the efficacy of acarbose versus buformin in NIDDM. Acarbose was found to reduce postprandial but not fasting blood glucose levels and to be slightly less effective than buformin. 

These drugs lower blood glucose by a variety of mechanisms. They are of no use in IDDM, but do have a place in the treatment of NIDDM. There are two main groups of oral hypoglycaemics the sulfonylureas and the biguanides. There are some newer drugs recently added or in development. 

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