Alpha-glucosidase inhibitors for people with impaired glucose tolerance or impaired fasting blood glucose

Alpha-glucosidase inhibitors (acarbose, miglitol, voglibose) are drugs that delay the breakdown of carbohydrates in the gut, and consequently slow down the absorption of sugars. Patients with type 2 diabetes may use it therapeutically. People with a raised blood glucose level (without being a diabetes patient) may use this drug in order to prevent developing type 2 diabetes and diabetes related morbidity such as cardiovascular diseases. To find evidence for these assumptions, we searched the medical literature for randomised controlled trials of at least one-year duration, investigating alpha-glucosidase inhibitors for patients with impaired glucose tolerance (IGT) or impaired fasting blood glucose (IFBG). Patients with IGT or IFBG have raised blood glucose levels, but do not meet the criteria for having type 1 or type 2 diabetes.
In our review we included five studies, representing 2360 participants, investigating acarbose. Of these studies, one was of high quality, and two did not show exact data, as the results were not available in full publication. The study of high quality yielded that if 10 people with IGT would take acarbose for three years, one case of diabetes would not occur. This finding was confirmed in studies of lower quality. The relevance of this finding is questionable because we found only small effects on blood glucose levels, and the mechanism behind this finding remains unclear: does acarbose really prevent diabetes does it delay the occurrence or mask type 2 diabetes? With respect to the effect on the occurrence of cardiovascular diseases, a dubious preventive effect of acarbose on the occurrence of myocardial infarctions was found. However, definitive conclusion could not be drawn and this latter finding should be confirmed in other studies. We found no statistically significant effects on the occurrence of death, other complications related to IGT, or quality of life. Side effects were mostly of gastro-intestinal origin (flatulence, diarrhoea).
The low number of studies, the poor quality of four of the included studies, and the missing data of two included studies limited this review. First, the missing data of two included studies need to be made available for a future update of this review. Next, the results of the two ongoing studies should be implemented in the review. If, after that, the evidence remains inconclusive, new trials should be initiated in order to investigate the true value of alpha-glucosidase inhibitors for patients with impaired glucose tolerance or impaired fasting blood glucose.

Authors' conclusions: 

There is evidence that acarbose reduces the incidence of type 2 diabetes in patients with IGT. However, it is unclear whether this should be seen as prevention, delay or masking of diabetes. Acarbose may prevent the occurrence of cardiovascular events, but this finding needs to be confirmed in more studies.

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Background: 

Alpha-glucosidase inhibitors (AGIs) reduce blood glucose levels and may thus prevent type 2 diabetes and cardiovascular disease in patients with impaired glucose tolerance (IGT). These possible effects, and the effects on quality of life, plasma lipids and body weight, have never been investigated in a systematic literature review and meta-analysis.

Objectives: 

To assess the effects of alpha-glucosidase inhibitors in patients IGT or impaired fasting blood glucose (IFBG), or both.

Search strategy: 

We searched The Cochrane Library, PUBMED, EMBASE, Web of Science, LILACS, databases of ongoing trials, reference lists of relevant reviews, and we contacted experts and manufacturers.

Selection criteria: 

Randomised controlled trials of at least one-year duration in patients with IGT or IFBG, or both, comparing AGI monotherapy with any other intervention.

Data collection and analysis: 

Two reviewers read all abstracts, assessed quality and extracted data independently. Discrepancies were resolved by consensus or by the judgement of a third reviewer.

Main results: 

We included five trials (2360 participants), all investigating acarbose, that included patients with IGT or patients 'at increased risk for diabetes' (n = 1). Study duration was one, three (n = 2), five and six years. One study was at low risk of bias and four studies at high risk of bias. Except for the outcome incidence of type 2 diabetes in acarbose versus no treatment (two studies), meta-analyses were not possible. Data from the study at low risk of bias suggests that acarbose decreases the occurrence of type 2 diabetes (NNT = 10), cardiovascular events (NNT = 50, based on 47 events, study not initially powered for this outcome), post-load blood glucose (-0.6 mmol/L, 95% CI -1.0 to -0.3) and body mass index (0.3 kg/m2, 95% CI -0.1 to -0.5). No statistically significant effects were observed on mortality, other morbidity, glycated haemoglobin, fasting blood glucose, lipids and blood pressure. The effects on the incidence of type 2 diabetes were confirmed in two studies at high risk of bias (OR 0.2, 95% CI 0.1 to 0.6). Adverse effects were mostly of gastro-intestinal origin (OR 3.5, 95% CI 2.7 to 4.4).

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