Acarbose NIDDM

The STOP-NIDDM trial followed 1429 patients with impaired glucose tolerance who were randomized to treatment with acarbose or placebo over 3 years. This trial demonstrated that normalization of glycemic control in subjects with impaired glucose tolerance significantly diminished cardiovascular risk. The acarbose-treated group had a significant reduction in the development of major cardiovascular events and hypertension. 

The STOP-NIDDM trial demonstrated that -glucosidase therapy in prediabetic persons successfully prevented a significant number of new cases of type 2 diabetes and helped restore beta-cell function, in addition to reducing cardiovascular disease and hypertension. Intervention with acarbose also reduced cardiovascular events in persons with diabetes. Diabetes and cardiovascular disease prevention may become a further indication for this class of medications. 

Chiasson JL et al Acarbose for prevention of type 2 diabetes mellitus The STOP-NIDDM randomized trial. Lancet 2002 359 2072. [PMID 12086760]... 

Chaisson JL et al Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance The STOP-NIDDM trial. JAMA 2003 290 486. 

In the STOP-NIDDM trial of acarbose cardiovascular risk and hypertension were reduced however, almost a quarter of the participants withdrew early, and the main cause of early withdrawal was gastrointestinal adverse effects (43). 

Odawara M, Bannai C, Saitoh T, Kawakami Y, Yamashita K. Potentially lethal ileus associated with acarbose treatment for NIDDM. Diabetes Care 1997 20(7) 1210-1. 

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. 

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. 

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). 

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. 

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. 

Macrovascular Complications. The STOP-NIDDM study demonstrated that acarbose can decrease the conversion rate of impaired glucose tolerance to diabetes, as well as reduce the risk of... 

In the STOP-NIDDM trial the incidence of newly diagnosed hypertension was reduced by 34%. In a meta-analysis of controlled long-term studies with acarbose (MeRIA), systolic blood pressure was reduced by 2.7 mmHg (p = 0.024) [36]. The synergistic effect of AGls on blood pressure may be the result of improved endothelial function due to protection from vasotoxic postprandial glucose spikes [37]. 

Hanefeld M, Fischer S, Schulze J et al. Therapeutic potentials of acarbose as first-line drag in NIDDM insufficiently treated with diet alone. Diabetes Care 1991 14 732-737. 

May C. Efficacy and tolerabihty of step wise increasing dosage of acarbose in patients with non-insuhn-dependent diabetes (NIDDM) treated with suUbnylureas. Diabetes Stoffwechsel 1995 4 3-7. 

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