REDUCTION OF THE ACUTE BIOAVAILABILITY OF METFORMIN BY THE ALPHA-GLUCOSIDASE INHIBITOR ACARBOSE IN NORMAL MAN

In a double-blind cross-over study, we investigated a possible influen ce of the alpha-glucosidase inhibitor acarbose on the bioavailability of the biguanide compound metformin. Each of the six healthy young mal e volunteers was randomly allocated during two consecutive 7 day perio ds to either acarbose (days 1-3: 3 x 50 mg day(-1); days 4-7: 3 x 100 mg day(-1)) or placebo. At day 7 and 14 of the study, the overnight-fa sted subjects ingested 1000 mg metformin with the first bite of a stan dardized breakfast (500 kcal; 60 g carbohydrates) and together with ei ther placebo or 100 mg acarbose. Acarbose significantly (P < 0.05) red uced the meal-induced increase in blood glucose and plasma insulin lev els. Acarbose induced a significant (P < 0.05) reduction in early (90, 120, 180 min) serum levels, peak concentrations (Cmax: 1.22 +/- 0.14 vs. 1.87 +/- 0.60 mg l(-1)) and area under the curve of metformin (AUC 0-540 min: 423 +/- 55 vs. 652 +/- 55 mg min l(-1)), but did not dimin ish its 24 h urinary excretion. In conclusion, acarbose significantly reduces the acute bioavailability of metformin in normal subjects.