VOGLIBOSE (AO-128) IS AN EFFICIENT ALPHA-GLUCOSIDASE INHIBITOR AND MOBILIZES THE ENDOGENOUS GLP-1 RESERVE

The alpha-glucosidase inhibitor voglibose (AO-128) was designed to pre vent rapid postprandial blood glucose rises in non-insulin-dependent d iabetics. We analyzed its effect on the enteroinsular axis in 72 healt hy volunteers in a double-blind study design before, after the ist dos e, and on the 7th day of a 7-day treatment protocol (3 daily loads). S ix 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 interv als up to 180 min after a standardized breakfast to analyze the levels of glucose, insulin, C peptide, gastric inhibitory polypeptide, and g lucagon-like peptide 1 (GLP-1). As expected, after ingestion of voglib ose, slight to moderate gastro-intestinal discomfort but no severe sid e-effects were reported. In a dose-dependent manner, voglibose signifi cantly 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 i ncrease of gastric inhibitory polypeptide was already reduced after th e first load of 2 and 5 mg voglibose. In comparison to the placebo gro up, this inhibition became also significant for the lower loads after 7 days. Interestingly, GLP-1, originating from the lower intestines, w as increasingly released under voglibose treatment. The first administ ration 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 an d thereby mobilizes the endogenous pool of insulinotropic GLP-1.