Glyburide in Women with Mild Gestational Diabetes

Ahroom Youk, Mercer University College of Pharmacy

Gestational diabetes mellitus (GDM) is defined by the American Diabetes Association (ADA) as glucose intolerance diagnosed in the second or third trimester of pregnancy that is not clearly overt diabetes.1  In 2014, the Centers for Disease Control and Prevention (CDC) reported that the prevalence of gestational diabetes in the United States may be up to 9.2%.  A study by CDC researchers discovered that the prevalence of gestational diabetes increased with increasing maternal age and number of children, but decreased with higher education.  They also reported that higher prevalence was found in Asian/Pacific Islanders and Hispanics (estimated to be 16.3% and 12.1%, respectively), and lower in non-Hispanic whites (6.8%).2

The Mayo Clinic lists the complications of untreated GDM in neonates as well as their mothers.  They state that complications in neonates include preterm birth, respiratory distress syndrome, excessive birth weight, hypoglycemia, and the development of type 2 diabetes mellitus later on in life.  Complications they include for the mother consist of high blood pressure, pre-eclampsia, and the development of type 2 diabetes mellitus later on in life.3

The ADA strongly recommends that pregnant women without a history of diabetes should test for GDM with a 75 g oral glucose tolerance test at 24-28 weeks of gestation.  Lifestyle interventions or metformin therapy is recommended in pregnant women with a history of GDM who are found to have prediabetes.  Additionally, the ADA’s position statement suggests that women should be tested for undiagnosed type 2 diabetes if they have risk factors from the standard diagnostic criteria.  In pregnant women with a history of GDM, the ADA recommends lifelong screening every three years.  In patients diagnosed with GDM, the ADA’s first-line recommendation is management with diet and exercise; if this fails to improve glycemic control, pharmacotherapy may be added as necessary.1

Title: Glyburide in Women with Mild Gestational Diabetes4
Design Randomized, placebo-controlled trial; N= 395
Objective To evaluate whether the addition of glyburide to diet therapy modifies pregnancy outcomes in women with mild gestational diabetes
Study Groups Glyburide 2.5 to 20 mg daily (n= 189); placebo (n= 186)
Methods Pregnant women with mild gestational diabetes and without a diagnosis of overt diabetes mellitus who were between 24 and 30 weeks of gestation were treated with either glyburide or placebo.  All women also received standardized education on nutrition and recommendations for their diet.  The glyburide group initially received 2.5 mg daily, which was titrated to a maximum of 20 mg daily based on their glucose values.  Their blood glucose measurements were checked four times daily.  A statistically significant result was defined as p< 0.05.
Duration 100 days
Primary Outcome Measure Decrement of birth weight by at least 200 g in neonates of mothers treated with glyburide
Baseline Characteristics
Characteristic Glyburide (n= 189) Placebo (n= 186) p-value
Age (years) 31.3 ± 6 31.2 ± 6 0.9
Race 0.7
     Hispanic 177 (93) 173 (93)
     White 6 (3) 7 (3)
     Black 3 (2) 1 (1)
     Other 3 (2) 5 (3)
Multiparous 151 (80) 155 (83) 0.4
Prepregnancy BMI (kg/m2) 29.0 ± 4.8 28.9 ± 5.3 0.8
Gestational age at enrollment (weeks) 26 ± 2 26 ± 1 0.8
50 g glucose screen result (mg/dL) 174 ± 22 172 ± 23 0.5
100 g glucose tolerance test values (mg/dL)
     Fasting 88 ± 9 89 ± 11 0.6
     One hour 205 ± 23 201 ± 21 0.1
     Two hours 186 ± 23 185 ± 21 0.8
     Three hours 140 ± 30 140 ± 30 1.0
Data are mean ± standard deviation or n (%) unless otherwise specified.
Results A decrement in birth weight of 200 g was not found; the mean birth weight in neonates of women treated with glyburide was 33 g lower compared with those treated with placebo (p= 0.52).
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: N/A
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions The addition of glyburide to diet therapy significantly improved maternal glycemic control over time when compared with placebo.  However, adding glyburide to diet did not decrease birth weight or improve maternal or neonatal outcomes in women with mild gestational diabetes.

This study was not without limitations; it was conducted at a single institution with a large Hispanic population.  Therefore, it cannot be generalized to the entire United States population.  Twenty patients did not deliver at the study institution or were lost to follow-up, for reasons not delineated by the authors.  Although therapy with glyburide significantly improved maternal glycemic control compared with placebo, it did not affect neonatal or pregnancy outcomes associated with gestational diabetes.  Furthermore, glyburide did not decrease the necessity of insulin therapy.  From this study, the authors concluded that glucose monitoring with diet therapy alone is the optimal therapy for women with mild gestational diabetes.4

 

References:

  1. The American Diabetes Association. Standards of Medical Care in Diabetes: Abridged for Primary Care Providers. 2015.
  2. DeSisto CL, Kim SY, Sharma AJ. Prevalence Estimates of Gestational Diabetes Mellitus in the United States, Pregnancy Risk Assessment Monitoring System (PRAMS), 2007–2010. Prev Chronic Dis. 2014;11:130415. DOI: http://dx.doi.org/10.5888/pcd11.130415
  3. The Mayo Clinic. Diseases and Conditions: Gestational Diabetes. Available at: http://www.mayoclinic.org/diseases-conditions/gestational-diabetes/basics/complications/con-20014854. Accessed August 11, 2015.
  4. Casey BM, Duryea EL, Abbassi-ghanavati M, et al. Glyburide in Women with Mild Gestational Diabetes: A Randomized Controlled Trial. Obstet Gynecol. 2015;126(2):303-9.
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