OBJECTIVE: To examine the impact on metabolic control in NIDDM patients of the alpha-glucosidase inhibitor, acarbose, when administered at a low dose in powdered form. RESEARCH DESIGN AND METHODS: Six subjects were recruited for a double-blind cross-over trial using 25 mg powdered acarbose and a placebo 3 times a day with meals for 3 mo. In addition to parameters of diabetes control and body weight, glucose turnover and insulin sensitivity were measured with the hyperinsulinemic/euglycemic clamp technique combined with tracer kinetics. RESULTS: None of the subjects showed significant changes in FPG levels or body weight either on the 3-mo course of acarbose or placebo. HbA1c fell significantly from 10.6 +/- 1.0 to 9.4 +/- 1.3% (P = 0.05) during treatment with acarbose but failed to change on placebo (10.1 +/- 1.0 to 11.1 +/- 2.0%; P = 0.36). Basal HGP and glucose utilization were unchanged during either of the treatment periods, and hyperinsulinemia produced a similar degree of suppression of HGP before and after each treatment. At a physiological concentration, insulin failed to stimulate glucose clearance in these diabetic patients, and no improvement was seen with acarbose treatment. No changes in plasma lipids or lipoprotein profiles were demonstrated after 3 mo on acarbose. In acute studies, it was shown that administration of acarbose at a dose of 25 mg powder per meal significantly decreased the postprandial glycemic excursion. CONCLUSIONS: When administered in the powdered form at the low dose of 25 mg 3 times/day with meals over 3 mo, acarbose was well tolerated by the NIDDM patients and was without side effects. It improved glycemic control by reducing postprandial hyperglycemia, but had no effect on glucose turnover, insulin sensitivity, or lipid profile.