Dose-Dependent Effects of Glyburide on Insulin Secretion and Glucose Uptake in Humans
- Leif C Groop, MD,
- Nir Barzilai, MD,
- Klaus Ratheiser, MD,
- Livio Luzi, MD,
- Elisabeth Wåhlin-Boll, PhD,
- Arne Melander, MD and
- Ralph A DeFronzo, MD
- Fourth Department of Medicine, Helsinki University Hospital Helsinki, Finland; the Diabetes Division, Department of Medicine, University of Texas Health Science Center at San Antonio San Antonio, Texas; and the Department of Clinical Pharmacology, University of Lund Lund/Malmö, Sweden
- Address correspondence and reprint requests to Leif C. Groop, MD, Fourth Department of Medicine, Helsinki University Hospital, Unioninkatu 38, SF-00170 Helsinki, Finland.
Abstract
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 ≤ 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.
- Received April 9, 1990.
- Revision received March 15, 1991.
- Accepted March 15, 1991.
- Copyright © 1991 by the American Diabetes Association
