Cardiovascular benefits and safety profile of acarbose therapy in prediabetes and established type 2 diabetes

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Abstract

Abstract
Dysglycaemic disease is one of the most important health issues facing the world in the 21st century. Patients with type 2 diabetes and individuals with prediabetes are at risk of developing macrovascular and microvascular complications. Long-term management strategies are therefore required that are effective at controlling dysglycaemia, well tolerated and, ideally, offer additional cardiovascular disease (CVD) risk-reduction benefits. The efficacy, safety and tolerability of the α-glucosidase inhibitor acarbose have been well-established in a wide range of patient populations in both clinical and community trials. In addition, acarbose has been shown to reduce cardiovascular complications in type 2 diabetes and prevent hypertension and CVD in individuals with impaired glucose tolerance (IGT). Acarbose has a very good safety profile and, owing to its straightforward, non-systemic mode of action, avoids most adverse events. The most common side-effects of acarbose are mild-to-moderate gastrointestinal complaints that subside as treatment continues. They can be minimised through the use of an appropriate stepwise dosing regimen and careful choice of diet. Acarbose is therefore a valuable option for the management of type 2 diabetes and, as the only oral antidiabetes agent approved for the treatment of prediabetes, can help to improve clinical management across the dysglycaemic disease continuum.

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Background
Cardiovascular disease (CVD) is the leading cause of mortality associated with dysglycaemia. Type 2 diabetes accounts for almost one in ten of all deaths around the world each year, and up to 80% of these deaths are CVD-related 1,2. Moreover, there is now substantial evidence to show that the prediabetic state of impaired glucose tolerance (IGT) is itself a significant CVD risk factor 3,4. Several management strategies have been proposed for the early stages of dysglycaemia, with the aim of preventing the development of type 2 diabetes and associated complications, such as CVD. A key strategy is lifestyle modification", involving changes in diet and exercise, which was shown in both the US Diabetes Prevention Program (DPP) and the Finnish Diabetes Prevention Study (DPS) to reduce the incidence of type 2 diabetes by 58% 5,6. However, although lifestyle modification is a vital part of dysglycaemia management, it is often insufficient to maintain long-term glycaemic control. In such cases, pharmacological intervention will be required; such treatment should place the minimum additional strain on a patient''s metabolic, endocrine and vascular systems. Consequently, several antidiabetes and other medications have been studied to determine their potential benefits in the prevention of type 2 diabetes. Results from trials of acarbose, metformin and rosiglitazone in prediabetic populations are summarised in Table 1. The Study to Prevent Non-Insulin Dependent Diabetes Mellitus (STOP-NIDDM) found that treatment with acarbose reduces the incidence of type 2 diabetes by 36% 7. In the DPP, treatment with metformin reduced the incidence of diabetes by 31%, although this effect was less marked in older patients, perhaps owing to age-related differences in insulin secretion 5,8. The DPP also found a significant reduction in the incidence of diabetes with troglitazone, another insulin sensitiser; however, troglitazone was discontinued before the end of the study owing to concerns regarding liver toxicity 9. More recently, the structurally related drug rosiglitazone was found to reduce the risk of type 2 diabetes and increase reversion to normal glucose tolerance when administered in addition to lifestyle modification 10. Although no liver toxicity was observed in this study, patients receiving rosiglitazone did have a significantly increased risk of chronic heart failure (p = 0.01) 11.

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