Glyburide and Metformin for Gestational Diabetes Mellitus (GDM)

Gestational diabetes mellitus (GDM) is a common complication of pregnancy. Multiple
treatment regimens are currently used for the management of GDM. Following failure of diet
therapy, insulin, glyburide and metformin are all used in the treatment of GDM with the oral
medications providing comparable outcomes with insulin but easier route of administration
and schedule. The proposed work will evaluate the pharmacokinetics (PK) and pharmacodynamics
(PD) of glyburide and metformin alone and in combination in order to lay the foundation in
establishing dosage and response information that could be utilized in designing a phase III
randomized trial that will ultimately evaluate GDM treatment optimization.

Inclusion Criteria:

Gestational Diabetes Subject Selection

1. Pregnant women (singleton pregnancy)

2. Gestational diabetes mellitus

3. Able to give written informed consent

4. Drug treatment is required for GDM

5. Gestational age 20-32 weeks

- Gestational diabetes diagnosis must occur after 20 weeks and prior to 32 weeks
gestation

- Randomization and treatment initiation must occur no later than 32 weeks
gestation

6. Willing to avoid ethanol

7. 18-45 years of age

Type 2 Diabetes Mellitus Subject Selection

1. Able to give written informed consent

2. New diagnosis of type 2 diabetes mellitus

3. Plan to receive metformin for treatment of type 2 diabetes mellitus

4. 18-45 years of age

5. Female

6. Negative pregnancy test

7. Hemoglobin A1C > 7%

Healthy Pregnant Women

1. Able to give written informed consent

2. Pregnant women (singleton)

3. Normal 1-hour glucose tolerance test

4. 20-32 weeks gestation

5. 18-45 years of age

Neonates: All the infants of the pregnant women participating in this study will be
included

Exclusion Criteria:

Women with GDM and T2DM

1. Women taking medications expected to interact with glyburide, metformin or alter
blood glucose concentrations

2. Serum creatinine > 1.2 mg/dL

3. Hematocrit < 28%

4. Allergy to glyburide, metformin or sulfa

5. Significant hepatic disease

6. Congestive heart failure or history of MI

7. Moderate to severe pulmonary disease

8. Adrenal or pituitary insufficiency

Healthy Pregnant Women

1. Receiving any hypoglycemic agents

2. Receiving corticosteroids

3. Known kidney, liver, heart, pulmonary, adrenal or pituitary disease

4. Hematocrit < 28%

Neonates

1. Infants that are not viable or too ill for blood sample collection will be included
for clinical outcomes data collection, but will be excluded from other research
activities.

2. Infants < 1.5 kg will be included for clinical outcomes data collection, but will be
excluded from blood sample collection.