Inhibition of sucrose- and starch-induced glycaemic and hormonal responses by the ?-glucosidase inhibitor emiglitate (BAY o 1248) in healthy volunteers

Abstract

The absorbable deoxynojirimycin derivative emiglitate (BAY o 1248) is a potent competitive inhibitor of small intestinal alpha-glucosidases in man. In two similar randomized, placebo-controlled, double blind investigations, the efficacy, duration of action and tolerability of single doses of 10, 20 and 40 mg emiglitate have been assessed in healthy male volunteers after repeated sucrose or maize-starch loads at 08.00, 12.00 and 17.00 h. Even at the lowest dose used, emiglitate almost abolished the glycaemic (-88%) and hormonal responses after the first sucrose meal, simultaneously evoking significant hydrogen evolution (mean peak H2-concentration greater than 100 ppm), which was not related to the dose, and which induced unacceptable symptoms of carbohydrate malabsorption, i.e. at the dosages tested, the inhibition of glycaemic and hormonal responses was at the expense of intolerable gastrointestinal adverse effects. Flattening of postprandial responses of blood glucose, serum insulin and gastric inhibitory polypeptide was still apparent after a second sucrose load 4 h later, demonstrating long-lasting inhibition of alpha-glucosidase activity. After starch, the dose dependency of inhibition emerged more clearly than after sucrose, i.e. the reduction was less pronounced. However, emiglitate led to significant reduction of the glycaemic and hormonal rises after both the first and second starch meals. Symptoms of carbohydrate malabsorption were absent after 10 mg and were negligible with 20 mg or 40 mg emiglitate. Breath hydrogen concentration increased gradually, indicating slight but significant carbohydrate malabsorption after the highest dose of the alpha-glucosidase inhibitor. The results show that a single morning dose of 20-40 mg emiglitate might be useful in the control of postprandial hyperglycaemia after breakfast and lunch.(ABSTRACT TRUNCATED AT 250 WORDS)