Abstract
In the emerging landscape of cardiovascular (CV) outcome trials evaluating the effects of blood glucose lowering drugs in individuals with type 2 diabetes, it is becoming increasingly apparent that since the promising signals coming from the United Kingdom Prospective Diabetes Study (UKPDS) no unequivocal benefits have been established for any single therapy thus far. There is an unmet need for introducing an effective pharmacological agent which could target both correlates of glycaemic regulation and CV risk factors, to ameliorate the enormous burden of fatal and non-fatal CV events in diabetic patients. Acarbose, like other alpha-glucosidase inhibitors (AGIs), has been proven to be an effective antidiabetic treatment for decades, but the overall significant impact of this class of drugs on modulating CV risk has only recently been appreciated. Accumulating evidence has shown that apart from its multiple effects on primarily postprandial glucose dysmetabolism, a key component of mechanisms linked to increased incidence of CV events, acarbose therapy also associates with a favorable impact on an array of surrogate markers of CV disease. Data stemming from in vitro testing of human cell lines as well as from preliminary trials in diabetic populations, like the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial, have highlighted – though not undisputed – the potential beneficial effects of the drug on CV morbidity. Large scale trials, like the ongoing Acarbose Cardiovascular Evaluation (ACE) trial, aim at conclusively establishing such a positive effect in patients with coronary heart disease and impaired glucose tolerance. In view of its usually acceptable level of side effects that are, if they occur, mostly limited to transient gastrointestinal symptoms, acarbose could well be a strong future player in CV disease secondary prevention. Current discouraging results from many trials of antidiabetic medications to significantly lower CV event rates in diabetic patients, should only draw further attention on alternative glucose lowering agents, among which acarbose is indeed promising.
Highlights
Unexpected – even adverse – cardiovascular (CV) outcome results of recent randomized controlled trials (RCTs) evaluating long term blood glucose lowering therapy in large patient cohorts with type 2 diabetes have gained worldwide attention [1,2]
The CV benefits seen with metformin therapy in a subset of overweight (>120% ideal boody weight) patients in the United Kingdom Prospecitve Diabetes Study (UKPDS, [5]), seem to be largely confined to the comparison without other antidiabetic drug treatment only or to younger patients, according to a recent meta-analysis including 35 RCTs [6]
The GLP-1 enhancing effect is seen in type 2 diabetic patients during standardized meal tests, when administration of alpha-glucosidase inhibitors (AGIs) generates significantly lower plasma glucose, serum insulin and total glucose-dependent insulinotropic polypeptide (GIP) levels, whereas concentrations of active GLP-1, the key incretin hormone, are significantly higher – up to 50% [33]. This notion has been recently reinforced by the finding that 24 weeks of acarbose monotherapy in newly diagnosed patients with T2D was associated with increased levels of both fasting and postprandial GLP-1, NO levels and NOS activity [37]; the benefits of acarbose on cardiovascular risk may, be related to its stimulation of GLP-1 secretion
Summary
Unexpected – even adverse – cardiovascular (CV) outcome results of recent randomized controlled trials (RCTs) evaluating long term blood glucose lowering therapy in large patient cohorts with type 2 diabetes have gained worldwide attention [1,2]. The GLP-1 enhancing effect is seen in type 2 diabetic patients during standardized meal tests, when administration of AGIs generates significantly lower plasma glucose, serum insulin and total GIP levels, whereas concentrations of active GLP-1, the key incretin hormone, are significantly higher – up to 50% [33] This notion has been recently reinforced by the finding that 24 weeks of acarbose monotherapy in newly diagnosed patients with T2D was associated with increased levels of both fasting and postprandial GLP-1, NO levels and NOS activity [37]; the benefits of acarbose on cardiovascular risk may, be related to its stimulation of GLP-1 secretion. Secondary outcomes include prevention of diabetes and all-cause mortality
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