We have studied the effect of sulfonylurea drugs on plasma free fatty acid and blood glucose concentrations in man. The concentrations of plasma free fatty acids and blood glucose were measured after the oral administration of a single dose of sulfonylurea drugs to fasting, maturity-onset, ketoacidosis-resistant diabetic patients. The changes in concentration of glucose and free fatty acids were not parallel as they are after systemic insulin or intravenous tolbutamide. There was no significant decrease in glucose concentration during the first hour after oral administration and little decrease at the second hour, but then a decrease to a minimum at five to six hours. During the first two hours, however, the concentration of free fatty acids decreased significantly despite little change in glucose concentration. At two hours, the concentration of free fatty acids decreased to its minimum, despite the fact that glucose concentration continued to decrease until five or six hours. These results are consistent with our earlier in vitro data and with the interpretation that the sulfonylurea drugs may have a direct antilipolytic effect.

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