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Glyburide for the Treatment of Gestational Diabetes

Glyburide is an oral medication of the sulfonyl-urea class  used to lower blood sugar. The drug acts by stimulating pancreatic islet cells to increase insulin secretion. Glyburide is highly bound to proteins in the blood. The action of glyburide may be enhanced by other drugs that are also highly protein bound such as beta blockers.

Pfizer lists glyburide (Micronase ®) as a pregnancy category B drug [1]. Other manufacturers list the drug as category C. Older studies did not show significant levels of glyburide in the blood of newborns whose mothers had taken glyburide during pregnancy or while breast feeding [2-4]. However, a study by the Obstetric-Fetal Pharmacology Research Unit Network showed the average fetal glyburide level to be 70% of the maternal level in women who took glyburide while pregnant [13]. Although glyburide has not been shown to have  harmful effects on the fetus to date, and appears to be an effective alternative to insulin in the treatment of gestational diabetes for some women the potential long-term effects on offspring are unknown.

Patients with diabetes prior to pregnancy, a history of diabetic ketoacidosis, liver disease, or a fasting blood sugar greater than or equal to 140 mg/dL are treated more appropriately with insulin [5-9]. Women with an OGTT less than 200 mg/dL, a fasting blood sugar less than 110 mg/dL, and who fail dietary therapy after 30 weeks gestation do well on glyburide therapy [9-12].

 The most commonly reported adverse events in patients taking glyburide have been nausea, heart burn, low blood sugar, muscle pain, joint pain, and allergic skin reactions including angioedema (swelling similar to hives) . Blurred vision has been reported with glyburide which is thought to be related to unstable blood sugar values. Liver problems including jaundice and hepatitis may also occur. Less commonly porphyria cutanea tarda, an abnormal sensitivity of the skin to sunlight, hyponatremia, a decrease in the number of agranulocyte white cells in the blood, thrombocytopenia, hemolytic anemia, aplastic anemia, and pancytopenia have been reported with sulfonylureas. Disulfiram-like reactions have been reported very rarely.[1]

Patients treated with glyburide for the control of gestational diabetes are classified as type A2 diabetes, and should receive the same antenatal surveillance as patients with A2 diabetes treated with insulin.
 

REFERENCES

1. Micronase® package insert 2002 www.pfizer.com/pfizer/download/uspi_micronase.pdf . Accessed 5/18/2007
2. Elliott BD, Langer O, Schenker S, Johnson RF. Insignificant transfer of glyburide occurs across the human placenta. Am J Obstet Gynecol 1991;165:807-812 PMID: 1951536
3. Elliott BD,  et al Comparative placental transport of oral hypoglycemic agents in humans: a model of human placental drug transfer. Am J Obstet Gynecol. 1994;171:653-60. PMID: 8092211
4. Feig DS, Briggs GG, Kraemer JM et al. Transfer of glyburide and glipizide into breast milk. Diabetes Care. 2005;28:1851-5. PMID: 16043722
5. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 30, September 2001.Gestational diabetes. Obstet Gynecol. 2001;98:525-38. PMID:11547793
6.Langer O, Conway DL, Berkus MD, Xenakis EM-J, Gonzalez O.A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med. 2000 ;343:1134-8.PMID: 11036118
7. Jacobson GF, et al. Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization. Am J Obstet Gynecol. 2005 Jul;193(1):118-24. PMID: 16021069
8. Langer O, et al. Insulin and glyburide therapy: dosage, severity level of gestational diabetes, and pregnancy outcome. Am J Obstet Gynecol.2005;192:134-9. PMID: 15672015
9. Kahn BF, et al., Predictors of glyburide failure in the treatment of gestational diabetes. Obstet Gynecol.2006;107:1303-9. PMID: 16738156
10. Rochon M , et al.,Glyburide for the management of gestational diabetes: risk factors predictive of failure and associated pregnancy outcomes. Am J Obstet Gynecol. 2006 ;195:1090-4. PMID:  17000241
11. Conway DL , et al., Use of glyburide for the treatment of gestational diabetes: the San Antonio experience. J Matern Fetal Neonatal Med. 2004 ;15:51-5.  PMID:15101612
12.Chmait R, et al. Prospective observational study to establish predictors of glyburide success in women with gestational diabetes mellitus.
J Perinatol. 2004;24:617-22. PMID: 15152273
13. Hebert MF,et al. Obstetric-Fetal Pharmacology Research Unit Network.Are we optimizing gestational diabetes treatment with glyburide? The pharmacologic basis for better clinical practice. Clin Pharmacol Ther. 2009 Jun;85(6):607-14.19295505  

SEE ALSO: DIABETES IN PREGNANCY
 

Created: 5/18/2007 Mark A Curran, MD
Updated: 3/21/10

 

 

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