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Dose-dependent effects of glyburide on insulin secretion and glucose uptake in humans
L C Groop1, N Barzilai, K Ratheiser
1Fourth Department of Medicine, Helsinki University Hospital, Finland.
Objective:
To examine the relationship between plasma glyburide concentrations (0, 50, 100, 200, 400, and 800 nM) and the insulin response and glucose metabolism during euglycemic (4.6 +/- 0.1 mM) and hyperglycemic (11.6 +/- 0.2 mM) conditions.
Research Design And Methods:
Nine healthy subjects participated in the study. Steady-state plasma glyburide concentrations were achieved by primed continuous intravenous infusion of glyburide.
Results:
During both euglycemia and hyperglycemia, glyburide enhanced insulin secretion and glucose disposal only to drug levels of 100-200 nM corresponding to an oral dose less than or equal to 10 mg.
Conclusions:
The data suggest that glyburide (and probably other sulfonylureas), operates within a narrow range of plasma concentrations (50-200 nM), which can be achieved with very low doses of the drug. It remains to be shown whether the threshold of maximal effect also in clinical practice is achieved with lower sulfonylurea doses than that currently used.