Alpha-glucosidase inhibitors 2012 – cardiovascular considerations and trial evaluation

Abstract

Alpha-glucosidase inhibitors have been available for clinical use for about 20 years. They have shown reasonably good efficacy comparable to other oral blood glucose lowering drugs and in some parts of the world are the most commonly prescribed oral diabetes medication, especially in Asian countries. Unlike as has been observed with some other blood glucose lowering agents, however, no adverse signals of potential cardiovascular harm have emerged in relation to their use. On the contrary, significant beneficial cardiovascular outcome results have been observed in the post-hoc analyses of randomised placebo-controlled trials with the alpha-glucosidase inhibitor acarbose. Targeting mainly postprandial hyperglycaemia, alpha-glucosidase inhibitors favourably affect several cardiovascular risk factors, such as obesity, hypertension and high glycaemic variability with little to no risk for hypoglycaemia. Furthermore, acarbose favourably affects endothelial dysfunction and carotid intima media thickening in humans and, in animal models, improves cardiac interstitial fibrosis and hypertrophy of cardiomyocytes. The ultimate determination of the cardiovascular effects of alpha-glucosidase inhibitors in terms of clinical outcomes awaits the results of ongoing long-term, randomised, placebocontrolled trials.

Impact of postprandial glucose control on diabetes-related complications: How is the evidence evolving?

“…The PPG-lowering effect of traditional α-glucosidase inhibitors -acarbose, miglitol and voglibose -has been attributed to the delay of carbohydrate absorption from the small intestine, which results in a blunting of the PPG excursion [74]. However, all of these therapies exert their action on basal as well as postprandial glucose, and none of them have been able to mimic the normal physiological postprandial response completely.…”

Antioxidant and α-glucosidase inhibitory activities of constituents from Euonymus alatus twigs

“…They are pseudo-carbohydrates that competitively inhibit ␣-glucosidase located in the brush border of enterocytes that hydrolyze oligosaccharides and polysaccharides into absorbable monosaccharides (Derosa and Maffioli, 2012). However, this mechanism of action can cause dose-related gastrointestinal side effects, such as abdominal distention, flatulence and diarrhea (Standl and Schnell, 2012). Furthermore, several postmarketing adverse reactions have been reported, which are less relevant to the mechanism of action of ␣-glucosidase inhibitors commercially available.…”

Therapeutic potential of α-glucosidase inhibitors in type 2 diabetes mellitus: an evidence-based review

“…Evidence suggests that AGIs directly or indirectly affects a number of CVD surrogate markers by reducing the level of PPHG [50,142,143]. In patients with T2DM, acarbose monotherapy can control inflammation, endothelial dysfunction and atherosclerosis by decreasing the activity of NFkB in the peripheral blood mononuclear cells through reduction of PPG peaks [144].…”