Efficacy of acarbose in Chinese subjects with impaired glucose tolerance

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Abstract

This multicentre, double-blind, placebo-controlled study investigated the efficacy of acarbose in Chinese individuals with impaired glucose tolerance (determined using a 75 g oral glucose tolerance test). Subjects were randomised to either placebo or acarbose 50 mg t.i.d. for a period of 16 weeks. Primary efficacy variables were the maximum postprandial plasma glucose value (Cmax) and the serum insulin profile. Secondary efficacy parameters included postprandial glucose profile, maximum postprandial insulin concentration (Cmax), changes in lipid profile and blood pressure and HbA1c and body weight and conversion to Type 2 diabetes. In the intention-to-treat analysis, acarbose treatment resulted in significantly higher reductions in postprandial glucose and serum insulin concentrations compared to placebo. Triglyceride concentration was the only lipid parameter to be significantly reduced in acarbose subjects. Loss of body weight was also significantly greater for acarbose than placebo subjects. Some 19 individuals converted to Type 2 diabetes (seven acarbose, 12 placebo), but this difference was not significant. Acarbose is efficacious in improving the metabolic state of individuals with impaired glucose tolerance indicating a potential benefit for the delay or prevention of onset of Type 2 diabetes in Chinese subjects.

Introduction

Diabetes is a major global health problem and an increasing cause of morbidity and mortality [1]. Impaired glucose tolerance (IGT), the metabolic stage intermediate between normal glucose homeostasis and diabetes, is clinically significant as a major risk factor for Type 2 diabetes [2] and cardiovascular disease (CVD) [3], [4]; it is part of a cluster of risk factors called the metabolic syndrome which includes obesity, hypertension and dyslipidaemia [5]. All these disorders are associated with insulin resistance and hyperinsulinaemia.

According to estimates [1], a 134% increase in diabetic adults is anticipated in China by 2025. An annual incidence rate of 15.7% was reported in the Chinese Da Qing study for the IGT control group [6] and an increased frequency of CVD and its risk factors was also shown in Da Qing IGT subjects [7]. As IGT incidence will probably increase with rising living standards in China, various intervention strategies should be tested.

The α-glucosidase inhibitor acarbose has shown beneficial effects on postprandial hyperglycaemia and hyperlipidaemia in Type 2 diabetic patients. These effects have been shown to be sustained during long-term therapy of up to 5 years duration [8], [9]. Furthermore, it has been proven that acarbose is well tolerated in Asian patients [10], [11], [12]. In addition, a study in Japanese Type 2 diabetic patients demonstrated that α-glucosidase inhibitors were more effective in conjunction with a diet rich in carbohydrates [13], although this topic is still in debate [14], [15]. For these reasons, acarbose might be an especially suitable agent for the Chinese population whose traditional diet is mainly composed of carbohydrates.

As there is evidence that Type 2 diabetes starts as a postprandial disease [16], [17], [18], [19], significant improvement in the surrogate parameters postprandial blood glucose and serum insulin in IGT subjects should then be able to prevent disease progression.

This study investigated the efficacy of acarbose to improve postprandial blood glucose and serum insulin profiles in Chinese IGT subjects.

Section snippets

Subjects and methods

The study was designed as a multicentre, double-blind, placebo-controlled, randomised parallel group comparison of acarbose and placebo. Subjects were recruited by five centres in the mainland of China; after obtaining written informed consent, the subjects were screened using the oral glucose tolerance test (75 g glucose) to determine if IGT defined according to WHO criteria (2 h-postprandial plasma glucose ≥140 mg/dl <200 mg/dl and fasting plasma glucose <125 mg/dl) was present. Further

Results

Of the 261 subjects randomised to the two treatment arms, three subjects did not receive double-blind study medication and were subsequently excluded from the safety analysis (acarbose n=126, placebo n=132). Six individuals were not valid for the ITT analysis (252 subjects; acarbose n=125, placebo n=127) and 247 subjects completed the study. Table 1 summarises the baseline demographic characteristics for the ITT population. The treatment arms compared well for all parameters; there was a small

Discussion

The development of Type 2 diabetes is usually preceded by a prediabetic phase of glucose levels above normal but below the diabetic threshold. There are many IGT subjects who present with elevated postprandial blood glucose concentrations but normal fasting values. Heine et al. [16] showed that the 2 h-postprandial blood glucose value was a significant predictor of progression from IGT to Type 2 diabetes. Other studies have also provided evidence [17], [18], [19]. The DECODE study also showed

Acknowledgements

The technical help of Dr Wen Wu, Medical Department of Bayer Healthcare Beijing, is gratefully acknowledged. This study was supported by Bayer AG, Leverkusen, Germany.

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