Management


The American College of Obstetricians and Gynecologists (ACOG) and the American Diabetes Association (ADA) have developed separate guidelines for managing GDM that emphasize the importance of glucose control to minimize the risk of complications.

Individualized nutritional therapy along with daily self-monitoring of glucose is the cornerstone of treatment. When dietary management fails to achieve glycemic control, both guidelines recommend that maternal hyperglycemia be managed medically. The ADA currently advocates the use of insulin in this circumstance.1


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After GDM has been diagnosed, the ADA recommend the following glucose goals:5

  • ≤95 mg/dL (5.3 mmol/L) and either:

  • One-hour postprandial ≤140mg/dL (7.8 mmol/L) or

  • Two-hour postprandial ≤120mg/dL (6.7 mmol/L)


Glyburide in pregnancy


Previous experience with first-generation sulfonylurea drugs in pregnancy, such as tolbutamide (Orinase, Tol-Tab) and chlorpropamide (Diabinese, Insulase), has not been encouraging. These drugs readily cross the placenta, resulting in the potential for neonatal hypoglycemia and fetal abnormalities.

Neonatal hypoglycemia may lead to fetal hyperinsulinemia, which is associated with many of the complications that occur in GDM (i.e., macrosomia, hypoxia and death).9 For this reason, several authoritative bodies advise against giving sulfonylurea drugs in pregnancy.


Results from a study conducted to measure the transport of a second-generation sulfonylurea, glyburide, across the human placenta in vitro, indicate that glyburide did not cross the placenta in significant amounts.10 This information has sparked new interest in its use during pregnancy.


In 2000, the first randomized controlled trial was performed to test the hypothesis that glyburide might be an alternative to insulin therapy in women with GDM. Of the 404 women in the study, 201 were assigned to receive glyburide, and 203 were assigned to receive insulin. The degree of glycemic control and the perinatal outcomes were essentially the same for both groups.11

There were no significant differences in mean maternal glucose concentrations, percentage of LGA infants, macrosomia, neonatal intensive care unit (NICU) admission or fetal anomalies. More importantly, glyburide was not detected in the cord serum of any infant.11 The results of this study suggest that glyburide may be considered as a clinical equivalent to insulin therapy. 


There have been few to no new randomized controlled trials conducted since this initial discovery, but researchers have performed a number of retrospective studies. Results indicate no consistent evidence of an increase in adverse maternal or neonatal outcomes with glyburide when compared to insulin therapy.12 There was no significant difference in birth weights, percentage of LGA infants, neonatal hypoglycemia, NICU admissions or pre-eclampsia.12

However, the failure to achieve glycemic goals with glyburide was approximaetely 20% higher in most clinical populations. Women who did not achieve target glycemic goals with the maximum dose of 20 mg/day where switched to insulin therapy. There were no significant differences in maternal or neonatal outcomes in women who were switched to insulin therapy. The most common predictor of treatment failure was pretreatment fasting glucose value >115mg/dL.12

Although this data may demonstrate glyburide’s clinical equivocacy with insulin in the treatment of GDM, there were notable limitations in the previous studies. The limitations consisted of small sample sizes, differences in study design, a lack of power analysis or effect size estimations for outcome measures, and varied definitions of hypoglycemia and other measures.1 These factors may have accounted for the lack of detectable differences in treatment outcomes. 



Conclusion


Proper treatment of GDM with tight glycemic control is essential for maternal and neonatal well-being. Current evidence does not exclude the use of glyburide as an alternative to insulin therapy, but because of the limited data, there is room for speculation.

Larger randomized controlled trials need to be performed before the use of glyburide in the treatment of GDM can be justified. If providers chose to implement this type of therapy, patients need to be informed of the current research and clearly understand the potential risks and benefits.

Mary Pittman, PA-C, is a physician assistant at Carl R. Darnall Army Medical Center in Fort Hood, Tex.

Judith Stallings, MHE, PA-C, is assistant professor and clinical medicine coordinator of the obstetrics and gynecology section in the physician assistant program at Georgia Health Sciences University in Augusta.


References


  1. Nicholson W, Bolen S, Witkop CT et al. Benefits and risks of oral diabetes agents compared with insulin in women with gestational diabetes: a systematic review. Obstet Gynecol. 2009;113:193-205. 

  2. American Diabetes Association. Standards of medical care in diabetes—2010. Diabetes Care. 2010;33 Suppl 1:S11-S61.
  3. PubMed Health. Glyburide. AHFS consumer medication information.
  4. American Diabetes Association. Gestational diabetes mellitus. Diabetes Care. 2004;27 Suppl 1:S88-S90. 
  5. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33 Suppl 1:S62-S69.
  6. Hicks P. Gestational diabetes in primary care. Medscape Womens Health. 2000;5:2. 

  7. Metzger BE, Gabbe SG, Persson B et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010;33:676-682.
  8. Alto WA. No need for glycosuria/proteinuria screen in pregnant women. J Fam Pract. 2005;54:978-983.
  9. Greene MF. Oral hypoglycemic drugs for gestational diabetes. N Engl J Med. 2000;343:1178-1179.
  10. Elliott BD, Langer O, Schenker S, Johnson RF. Insignificant transfer of glyburide occurs across the human placenta. Am J Obstet Gynecol. 1991;165:807-12.

  11. 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.

  12. Moore TR. Glyburide for the treatment of gestational diabetes. A critical appraisal. Diabetes Care. 2007;30 Suppl 2:S209-S213. 

All electronic documents accessed November 10, 2011.