Are we optimizing gestational diabetes treatment with glyburide? The pharmacologic basis for better clinical practice

Clin Pharmacol Ther. 2009 Jun;85(6):607-14. doi: 10.1038/clpt.2009.5. Epub 2009 Mar 18.


Glyburide's pharmacokinetics (PK) and pharmacodynamics have not been studied in women with gestational diabetes mellitus (GDM). The objective of this study was to assess steady-state PK of glyburide, as well as insulin sensitivity, beta-cell responsivity, and overall disposition indices after a mixed-meal tolerance test (MMTT) in women with GDM (n = 40), nonpregnant women with type 2 diabetes mellitus (T2DM) (n = 26), and healthy pregnant women (n = 40, MMTT only). At equivalent doses, glyburide plasma concentrations were approximately 50% lower in pregnant women than in nonpregnant subjects. The average umbilical cord/maternal plasma glyburide concentration ratio at the time of delivery was 0.7 +/- 0.4. Insulin sensitivity was approximately fivefold lower in women with GDM as compared with healthy pregnant women. Despite comparable beta-cell responsivity indices, the average beta-cell function corrected for insulin resistance was more than 3.5-fold lower in women with glyburide-treated GDM than in healthy pregnant women. Women with GDM in whom glyburide treatment has failed may benefit from alternative medication or dosage escalation; however, fetal safety should be kept in mind.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Area Under Curve
  • Aryl Hydrocarbon Hydroxylases
  • Blood Glucose / analysis
  • Cytochrome P-450 CYP2C9
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes, Gestational / drug therapy*
  • Dose-Response Relationship, Drug
  • Female
  • Fetal Blood / chemistry
  • Glyburide / pharmacokinetics
  • Glyburide / therapeutic use*
  • Humans
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Resistance
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / physiology
  • Metabolic Clearance Rate
  • Monte Carlo Method
  • Pregnancy
  • Pregnancy Trimester, Third


  • Blood Glucose
  • Hypoglycemic Agents
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • Glyburide