Serum 1,5-anhydroglucitol (1,5AG) is a useful glycemic marker in the control of diabetes; however, treated with alpha-glucosidase inhibitors (alpha-GIs), acarbose (Aca) and voglibose (Vog), it tends to show the discrepancy between serum 1,5AG and related glucose levels. Twenty patients were randomly assigned to adding Aca or Vog to the current treatment. We measured serum 1,5AG levels and other parameters of diabetic control before, 2 and 4 weeks after the alpha-GI treatment. We also measured urinary 1,5AG levels using gas chromatography/mass spectrometry (GC/MS). Glycated albumin, Hb(A1c), and fasting plasma glucose (FPG) levels were significantly decreased after 2 and 4 weeks of treatment, and the changes were similar in the two groups. Despite the similar urinary excretion of 1,5AG and other glycemic parameters, serum 1,5AG level was significantly lower in the Aca group than in the Vog group (3.4+/-0.5 vs. 7.9+/-1.2 microg/ml, P<.005; mean+/-S.E.) at the period of 4 weeks. Even in the same glycemic level, the less increase of serum 1,5AG after treatment with Aca might be due to a reduction of intestinal 1,5AG absorption via inhibition of alpha-amylase that features Aca.