The effect of newα-glucosidase inhibitors (BAY m 1099 and BAY o 1248) on meal-stimulated increases in glucose and insulin levels in man

Abstract

To confirm findings obtained from animal experiments demonstrating the metabolic effect of two new glucosidase inhibitors, 7 single blind cross-over studies with 42 healthy male volunteers were performed. In each group 6 subjects received 25, 50, 100 and 200 mg BAY m 1099 and 10, 20, and 40 mg BAY o 1248 or placebo with a standardized breakfast. Blood glucose and serum insulin were measured in venous blood before and 30, 60, 90, 120 and 180 min after each of 3 meals. ECG, blood pressure, body weight, monitor ECG and haematological and clinico-chemical parameters were also examined. The postprandial increase in blood glucose and serum insulin after breakfast were significantly and dose-dependently reduced by BAY m 1099. 10 and 20 mg BAY o 1248 not only reduced the increases in blood glucose and serum insulin after breakfast, but also after lunch (10 mg). 40 mg BAY o 1248 prevented the postprandial increase in both metabolic parameters after breakfast (p less than 0.05), an effect which was sustained after lunch. Intestinal problems occurred (flatulence, meteorism, diarrhoea) in 25 of 42 volunteers. Objective tolerability was good. The results of these first clinical pharmacological studies with two new glucosidase inhibitors justify studies on patients with diabetes mellitus.

Inhibition of Glycemic and Hormonal Responses after Repetitive Sucrose and Starch Loads by Different Doses of the α-Glucosidase Inhibitor Miglitol (BAY m 1099) in Man

“…This investigation, confirming and ex tending the results of others [21,22,31], indicates that a single dose of miglitol in the morning is effective in reducing glycemic responses during the next 4 h. The doseresponse relationships, monitoring of breath Hi responses and subjective tolerability sug gest that 25-50 mg is the most suitable ther apeutic dose. However, the duration of ac tion (< 4 h) renders the application of 25 or 50 mg of miglitol at the main meals neces sary.…”

A Novel Synergistic Galactomannan-Based Unit Dosage Form for Sustained Release of Acarbose

“…Acarbose reduces serum triglycerides significantly in both rats and humans (24,52,53). This effect is mainly associated with a decreased hepatic very low-density lipoprotein triglyceride secretion rate which is also known to lead to a slight decrease in serum cholesterol concentrations.…”

“…Postprandial blood glucose levels were determined for all the groups at regular time intervals (0, 1,2,4,7,9,11,24,28,32,36,48,52,56,60, and 72 h) in the following study and the results are compiled in Fig. 6.…”

“…Various clinical trials conducted in patients with non-insulin-dependent diabetes mellitus indicate that acarbose is a potential drug which reduces postprandial glucose levels significantly along with a marked effect on the hypertriglyceridaemia, which is closely linked to carbohydrate and insulin metabolism (22,23). However, during treatment with these systems, approximately 50% of the patients report gastrointestinal side effects of flatulence, abdominal distension, borborygmus, and diarrhea (24). Development of a modifiedrelease system of acarbose (having a dose of 25-100 mg is to be taken at least thrice daily) will obviate the need of multiple dosing of the drug candidate and hence improve patient compliance with reduced gastrointestinal side effects by sustaining the release.…”

The role of lipid and carbohydrate digestive enzyme inhibitors in the management of obesity: a review of current and emerging therapeutic agents

“…147 In support of findings obtained from animal experiments, BAY o 1248 (10 mg) and BAY m 1099 (50 mg) delayed sucrose absorption and prevented post prandial increases in glucose in healthy male volunteers. 148 However, 60% of participants reported intestinal side effects such as flatulence and diarrhea, 149 an undesirable effect due to increased amounts of fermentable (undigested) carbohydrates.…”