Low-dose oral glyburide reduces glucose production rates in patients with impaired fasting glucose

Abstract

Impaired fasting glucose (IFG) is commonly seen in the US population. Approximately 20% of patients with IFG can progress to develop type 2 diabetes mellitus (DM-2) within 1 year. In the recent diabetes prevention study, lifestyle changes reduced the progression to only 8% per year, and metformin reduced the progression from IFG to DM-2 from 20% to 11% per year. Sulfonylurea therapy in DM-2 increases beta-cell function and fails to accelerate the 4% loss in function observed per year. Low-dose sulfonylurea therapy for IFG may be an effective treatment to delay the onset of type 2 diabetes if the treatment does not cause hypoglycemia. A very low dose of glyburide (20 microg/kg body weight) was given orally to 15 nondiabetic volunteers in an attempt to describe its effects on glucose production rates (GPR), blood glucose concentrations, and conterregulatory hormone profile. Six of the volunteers had IFG (mean +/- SEM, 115 +/- 1.8 mg/dL), and 9 had a normal fasting glucose (NFG) (94 +/- 2.3 mg/dL). Fasting blood glucose (FBG) decreased more in IFG after glyburide when compared with the NFG group (29% +/- 2.4% v 17% +/- 3.5%, P <.05). Patients with IFG had a larger insulin response to glyburide than those with NFG (17.7 +/-3 v 10.7 +/- 2.9 microU/mL; P <.05). The IFG patients also had a greater decrease in GPR (19% +/- 4%) than seen with the normals (12% +/- 3%, P <.05). The steeper decrease in GPR may have been due to a greater insulin response to oral glyburide in those with IFG. Low-dose glyburide increases insulin's effect on the liver.