European study on dose-response relationship of acarbose as a first-line drug in non-insulin-dependent diabetes mellitus: efficacy and safety of low and high doses.
The aim of this double-blind, placebo-controlled, multinational, five-arm study was to investigate the dose-response relationship of acarbose as a first-line drug in the treatment of type 2 diabetes (non-insulin dependent) over a range of minimal and maximal doses according to the European recommendations. The study included 495 patients from 7 countries who were insufficiently controlled with diet alone (glycosylated haemoglobin HbA1C 6.5%-9%). Acarbose, 25, 50, 100 or 200 mg t.i.d., or placebo t.i.d. was given for 24 weeks. Even a low dosage of 25 mg t.i.d. acarbose reduced fasting and postprandial blood glucose levels (1 h postprandial -11.6%; 2 h postprandial -11.3%). Acarbose in a dosage of 200 mg t.i.d. had the greatest effect on these parameters. In the placebo group the mean 2 h postprandial area under the curve (AUC) value for blood glucose was 22.6 mmol/l after 24 weeks' therapy. The mean 2 h postprandial AUC values in the patients given acarbose at doses of 25, 50, 100 and 200 mg t.i.d. were found to be 21.2, 19.6, 20.3 and 18.5 mmol/l, respectively. The corresponding HbA1C values for the placebo and acarbose groups were 7.83%, 7.37%, 7.08%, 6.98% and 6.79%. Interestingly, there was a plateau of blood glucose level at a dosage of 50-100 mg t.i.d. The frequency of flatulence decreased with the duration of drug therapy, but we could not find a linear relationship between doses of acarbose and the gastrointestinal side effects. Less than 3% of patients stopped tablet intake due to adverse events.
Fischer
S
S
Institute and Outpatient Department of Clinical Metabolic Research, Medical Faculty C. G. Carus, Technical University Dresden, Germany.
Hanefeld
M
M
Spengler
M
M
Boehme
K
K
Temelkova-Kurktschiev
T
T
D020909:Acarbose; D000328:Adult; D000368:Aged; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D014312:Trisaccharides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D020909:Acarbose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D014312:Trisaccharides