Voglibose (AO-128) Is an Efficient α-Glucosidase Inhibitor and Mobilizes the Endogenous GLP-1 Reserve

Abstract

The α-glucosidase inhibitor voglibose (AO-128) was designed to prevent rapid postprandial blood glucose rises in non-insulin-dependent diabetics. We analyzed its effect on the entero-insular axis in 72 healthy volunteers in a double-blind study design before, after the 1st dose, and on the 7th day of a 7-day treatment protocol (3 daily loads). Six parallel groups of 12 volunteers received voglibose (0.5, 1.0, 2.0, or 5.0 mg) or placebo (two groups). Blood was drawn at regular intervals up to 180 min after a standardized breakfast to analyze the levels of glucose, insulin, C peptide, gastric inhibitory polypeptide, and glucagon-like peptide 1 (GLP-1). As expected, after ingestion of voglibose, slight to moderate gastro-intestinal discomfort but no severe side-effects were reported. In a dose-dependent manner, voglibose significantly reduced postprandial increases of blood glucose, insulin, and C peptide. At the lower loads (0.5 and 1 mg voglibose three times daily), these effects were more pronounced after 7 days. The postprandial increase of gastric inhibitory polypeptide was already reduced after the first load of 2 and 5 mg voglibose. In comparison to the placebo group, this inhibition became also significant for the lower loads after 7 days. Interestingly, GLP-1, originating from the lower intestines, was increasingly released under voglibose treatment. The first administration of 1 mg voglibose enhanced GLP-1 secretion > 80% above controls. Treatment with 1 mg voglibose three times daily over 7 days revealed a maximal mobilizing effect on endogenous GLP-1 ( > 90% above controls) which was not further increased by 2- or 5-mg loads. We conclude that voglibose treatment effectively inhibits intestinal disaccharidases and thereby mobilizes the endogenous pool of insulinotropic GLP-1.

Comparison of Efficacies of a Dipeptidyl Peptidase IV Inhibitor and α-Glucosidase Inhibitors in Oral Carbohydrate and Meal Tolerance Tests and the Effects of Their Combination in Mice

“…Acarbose (28,29), voglibose (30), and miglitol (31) have been shown to enhance the GLP-1 response in healthy volunteers and type 2 diabetic patients. It is possible that the difference of GLP-1 levels between our study and these papers is due to the difference of the determination methods of GLP-1.…”

Response of low active GLP-1 like substances to test meal in obese Japanese patients with type 2 diabetes mellitus compared with obese controls with normal glucose tolerance

“…In the patients by this study, there was no significant differences (r = 0.01, p = 0.643, n = 24) in the association of AUCs in p-active GLP-1-S levels and the duration of diabetes from discovery. Furthermore, sulfonylurea [17,18] or thiazolizinedione [19] used did not decrease secretion of active GLP-1, whereas alpha-glucosidase inhibitors [20] or biguanide [21] may enhance secretion of active GLP-1. Hence, the p-active GLP-1 levels in patients treated with alpha-glucosidase inhibitors (n = 6) or biguanide (n = 18) in this study should result in higher than those in control.…”

Effect of co-administration of voglibose and vildagliptin on diabetic albino rats

“…The increased active GLP-1 level in the colon has significant correlation with ~ 1.4 fold increase in gut gene expression levels of neurod 1 and ~2.6-3.1 fold increase in glucagon, thereby increases the release of the glucoregulatory hormone glucagon like peptide-1 (GLP-1) into the circulation which contribute to their glucose lowering effect, may have boosting effect on the gliptins. 16,17 Also Chronic administration of voglibose resulted in a 40-51% decrease in plasma DPP-4 activity. 16 In clinical studies , alpha glucosidase inhibitors was found to reduce HBA1c by 0.5-0.8% , fasting glucose by ~1 mm and postprandial glucose by 2.0-2.5 mm.…”