ABSTRACT
AIMS: A double-blind randomised study was performed to compare the dose-effect and dose-tolerability relationships between the alpha-glucosidase inhibitor miglitol in doses of 25 mg, 50 mg, 100 mg and 200 mg all t.i.d. vs placebo t.i.d. in patients with Type 2 diabetes mellitus on diet only. METHODS: After a 6-week placebo run-in period 468 patients with a fasting blood glucose > or = 7 mmol/l as well as a HbA1c between 6.1% and 10.4% were randomised for a 24-week treatment period. RESULTS: The results of 465 patients were valid for safety analysis and of 384 patients for the efficacy analysis. In the placebo group the HbA1c level increased by 0.40+/-1.46% as compared with baseline. The decrease in the mean HbA1c values (corrected for differences in baseline values) was significant and dose-dependent for all miglitol groups compared with placebo, being -0.46% (95% CI: -0.91%, -0.01%) in the 25 mg group, -0.45% (95% CI: -0.90%, -0.003%) in the 50 mg group, -0.84% (95% CI: -1.31%, -0.37%) in the 100 mg group and -1.26% (95% CI: -1.76%, -0.76%) in the 200 mg group. Blood glucose levels following a standardised breakfast tolerance test were significantly and dose-dependently lower for all the miglitol doses at 12 and 24 wk of treatment compared to baseline: in comparison with baseline maximum blood glucose increased by 4% with placebo and decreased by 7%, 14%, 24% and 33% with miglitol 25 mg, 50 mg, 100 mg and 200 mg t.i.d. respectively. The same pattern was seen with postprandial maximal serum insulin levels which decreased by 8% under placebo and by 17%, 26%, 25% and 35% with the 25 mg to 200 mg doses of miglitol. The adverse events reported were mainly of gastrointestinal nature, mostly being flatulence, diarrhoea and abdominal pain and the incidence increased with increasing dose. Although the side effects were not serious, they were troublesome, leading to a considerable drop-out rate increasing with dose. CONCLUSIONS: The alpha-glucosidase inhibitor miglitol in Type 2 diabetic patients on diet alone decreases both HbA1c levels and postprandial glucose and insulin levels in a dose-dependent manner. Gastrointestinal side effects also showed dose-dependency. Combination of efficacy and safety results leads to the conclusion that the optimal dose of miglitol will be in the range of 50 to 100 mg t.i.d.
