glucose production and release and

glucose production and release and indirectly by increasing peripheral tissue sensitivity to insulin (27); miglitol acts at thesmall intestine by delaying the digestionof complex carbohydrates (28). Interestingly, patients receiving metformin plusmiglitol combination therapy tended tolose more weight than those on the othertreatment regimens (4). Weight loss mayindirectly improve glycemic control bydecreasing insulin resistance (29), whichmight have been another positive contributory factor to the superiority of themetformin plus miglitol combinationtherapy. Although combination therapydid not have any significant effect on fasting plasma insulin compared with metformin alone (212.4 6 3.8 vs. 217.4 64.7 pmol/l; P 5 NS), it did have a tendency to decrease the postprandial incremental plasma insulin area under thecurve (AUC) (260.1 6 19.4 vs. 10.5 617.7 pmol z h/l; P 5 0.059). This is probably caused by the effect of miglitol because miglitol alone resulted in a decreasein postprandial plasma insulin AUC of272.8 6 21.9 pmol z h/l. The reductionin postprandial plasma glucose and insulin could result in improved insulin sensitivity, as we have shown in elderly type2 diabetic subjects with acarbose treatment (30).Monotherapy with miglitol alone resulted in a treatment effect of 20.37% inHbA1c compared with placebo (Fig. 1).This is a much smaller effect than thatobserved in previously reported studies(11,13,22,23,31), in which a reduction inHbA1c between 0.74 and 1.19% wasshown. It is interesting that Johnston et al.(11) could not show any better efficacy ofmiglitol 100 mg three times a day compared with 50 mg three times a day. However, postprandial plasma glucose waslower after 100 mg three times a day onthe test meal. It is possible that the discordance between HbA1c and postprandialplasma glucose was caused by the lowercompliance at 100 mg three times a daybecause of increased gastrointestinal sideeffects. Similarly, in the present study, theeffect of miglitol on incremental postprandial plasma glucose AUC during thetest meal was significantly greater thanwith metformin alone (234.7 6 7.2