K. Ojima, Y. Kiyono, M. Kojima
2004
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Journal
Nihon yakurigaku zasshi. Folia pharmacologica Japonica
Abstract
Mitiglinide calcium hydrate (mitiglinide, Glufast) is a new insulinotropic agent of the glinide class with rapid onset. Mitiglinide is thought to stimulate insulin secretion by closing the ATP-sensitive K(+) (K(ATP)) channels in pancreatic beta-cells, and its early insulin release and short duration of action would be effective in improving postprandial hyperglycemia. In studies of various cloned K(ATP) channels, mitiglinide shows a higher selectivity for the beta-cell type of SUR1/Kir6.2 than the cardiac and smooth muscle types of K(ATP) channels in comparison with glibenclamide and glimepiride. In vitro and in vivo studies demonstrated the insulinotropic effect of mitiglinide is more potent than that of nateglinide, and mitiglinide surpassed in controlling postprandial hyperglycemia in normal and diabetic animals. In clinical trials, treatment with mitiglinide provided lasting improvement of postprandial hyperglycemia in Type 2 diabetic patients and decreased the fasting plasma glucose levels and HbA(1C) values. The incidence of adverse events related to mitiglinide were nearly equivalent to placebo; in particular there was no difference with the frequency of hypoglycemia. The results from these studies indicated that mitiglinide could be expected to possess good therapeutic features of being effective in reducing postprandial glucose excursions in the early stage of Type 2 diabetes and less incidence of events suggestive of hypoglycemia.