REDUCTION OF GLYCOSYLATED HEMOGLOBIN AND POSTPRANDIAL HYPERGLYCEMIA BY ACARBOSE IN PATIENTS WITH NIDDM - A PLACEBO-CONTROLLED DOSE-COMPARISON STUDY

OBJECTIVE - To compare the safety and efficacy of three doses of acarb ose (100, 200, and 300 mg three times daily) with placebo for the trea tment of non-insulin-dependent diabetes mellitus (NIDDM) in patients m aintained on dietary therapy alone. RESEARCH DESIGN AND METHODS - This multicenter double-blind placebo-controlled trial was 22 weeks in dur ation. The trial consisted of a 2-week screening period, a 4-week plac ebo run-in period, and a 16-week double-blind treatment period. The pr imary measure of drug efficacy was the mean change from baseline in Hb A(1c) levels. Additional efficacy variables included the mean change f rom baseline in fasting and postprandial plasma glucose and serum insu lin levels. RESULTS - After 16 weeks of treatment, acarbose-treated pa tients had statistically significant reductions in mean HbA(1c) levels of 0.78, 0.73, and 1.10% (relative to placebo) in the 100-, 200-, and 300-mg t.i.d. groups, respectively. Significant reductions in fasting and postprandial plasma glucose levels, glucose area under the time-c oncentration curve, and maximum glucose concentration were also observ ed in acarbose-treated patients. Although there were no statistically significant differences among the 100-, 200-, and 300-mg treatment gro ups, there was a trend toward a dose-response relationship for most pl asma glucose variables that were measured. Gastrointestinal side effec ts (e.g., abdominal pain, flatulence, and diarrhea) and serum transami nase elevations (e.g., aspartate aminotransferase [AST] and alanine am inotransferase [ALT]) were more frequently reported in the acarbose-tr eated patients than in the placebo-treated control patients. Transamin ase elevations occurred only at the 200- and 300-mg dosages and were r eadily reversible on discontinuation of treatment. CONCLUSIONS - Acarb ose at doses of 100, 200, and 300 mg administered three times daily fo r 16 weeks significantly reduced HbA(1c) levels and postprandial hyper glycemia. Treatment with acarbose is a safe and effective adjunct to d ietary therapy for the treatment of NIDDM.