Retardation of meal carbohydrate absorption by inhibition of starch degradation improves glucose tolerance in normal and diabetic humans. To determine the effects of Bay-m-1099, a new alpha-glucosidase inhibitor, on insulin requirements and prandial glucose tolerance in patients with insulin-dependent diabetes mellitus (IDDM), plasma glucose, triglyceride, and free insulin concentrations were measured after ingestion of a standard breakfast, lunch, and dinner in nine patients with IDDM in a single-blind, randomized, crossover design. A 20% reduction in insulin was given 30 minutes before the meals when the subjects received Bay-m-1099 (50 mg). This resulted in the AUC for plasma insulin to be significantly less with Bay-m-1099 (AUC, 8.2 +/- 1.3 vs. 12.8 +/- 1.6 microU/ml/min with placebo; P less than 0.01). Despite this reduction in plasma insulin levels, postprandial plasma glucose concentrations were reduced for the breakfast (73 +/- 15 vs. 112 +/- 14 mg/dl/min with placebo; P less than 0.01) and dinner (23 +/- 8 vs. 4 +/- 1 mg/dl/min with placebo; P less than 0.05) meal with Bay-m-1099. Bay-m-1099 did not affect postprandial plasma triglycerides and was well tolerated, the major side effect being flatulence (4/9) and mild diarrhea (4/9). We conclude that inhibition of intestinal alpha-glucosidases by Bay-m-1099 in IDDM reduces meal insulin requirements by at least 20% and that such an agent could be useful in the management of diabetes mellitus by reducing hyperinsulinemia.