Low-dose oral glyburide reduces fasting blood glucose by decreasing hepatic glucose production in healthy volunteers without increasing carbohydrate oxidation.

Glyburide is an effective hypoglycemic agent in patients with type II diabetes even after the loss of its ability to increase insulin secretion. The exact mechanism is unknown. In an attempt to describe the direct effect of glyburide on glucose metabolism, a very low dose of glyburide (20 micrograms/kg body weight) was given orally to 12 healthy volunteers in an attempt to increase blood concentrations of the drug without causing a marked increase in insulin secretion. Fasting hepatic glucose production (HGP), carbohydrate oxidation (CO), leucine appearance, leucine oxidation, and fat oxidation were determined between hours 3 and 4 and hours 7 and 8. The changes seen in the glyburide-treated volunteers were compared with the changes seen in 5 non-treated, healthy volunteers during the same 8-hour period. Mean blood glucose decreased greater in the glyburide-treated volunteers (20 +/- 2% vs 5 +/- 2%, P < 0.01). Insulin and C-peptide concentrations after glyburide administration (hour 7 to 8) did not differ significantly from baseline (hour 3 to 4) values (insulin: 53 +/- 9 pmol/L vs 52 +/- 9 pmol/L; C-peptide: 0.34 +/- 0.06 ng/mL vs 0.39 +/- 0.07 ng/mL). This low dose of glyburide resulted in a significantly greater decrease in HGP (16 +/- 2%; P < 0.001) than seen with fasting alone (8 +/- 4%; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)