Metformin Versus Insulin in Pregnant Women With Type 2 Diabetes

Official Title: “A Randomized, Controlled Trial of Metformin Versus Insulin in Women With Type 2 Diabetes Mellitus During Pregnancy in a Population With Severe Health Disparities”

Pregnant women with type 2 diabetes mellitus (T2DM) are at increased risk for miscarriages, birth defects, large infants, and stillbirths. Maintaining blood sugars in the normal range decreases these pregnancy complications. We hypothesize that metformin will achieve similar levels of blood sugar control compared to insulin. In doing so, metformin will prevent the increased risk of pregnancy complications associated with T2DM in pregnancy. We propose a pilot study of a randomized, controlled trial of metformin versus insulin in the treatment of T2DM during pregnancy.

Pregnant women with type 2 diabetes mellitus (T2DM) are at increased risk for miscarriages, birth defects, large infants, and stillbirths. Maintaining blood sugars in the normal range decreases these pregnancy complications. Currently, insulin is the primary medication used to treat pregnant women with T2DM. However, it is administered by injection several times a day and compliance is low in health disparity populations with high rates of obesity and diabetes. Insulin also has the potential to lead to dangerously low blood sugars.

Metformin is a medication than can be administered as pills and is not associated with dangerous low blood sugars. In addition, this insulin sensitizer is the medication of choice for women who are obese and have T2DM outside of pregnancy. We hypothesize that metformin will achieve similar levels of blood sugar control compared to insulin. In doing so, metformin will prevent the increased risk of pregnancy complications associated with T2DM in pregnancy. The aims of this study is to determine if in pregnant women with T2DM, metformin achieves similar glycemic control, and similar maternal and neonatal outcomes when compared to insulin. We propose a pilot study of a randomized, controlled trial of metformin versus insulin in the treatment of T2DM during pregnancy.

Intervention(s) in this Clinical Trial

• Drug: Metformin
  • Metformin 500 mg orally daily increased as needed to maintain glycemic control until a maximum of 2500 daily
• Drug: Insulin (NPH and Regular)
  • Insulin will be administered based on maternal gestational age and maternal weight using NPH and Regular insulin. It will be administered subcutaneously 3 times a day

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Metformin
  • Metformin therapy
• Active Comparator: Insulin
  • Insulin

Primary Measures

• The rate of achieving a hemoglobin A1C <7%
  • Time Frame: at the time of delivery
    Safety Issue?: No

Secondary Measures

• Body mass index
  • Time Frame: At delivery
    Safety Issue?: No
• Hypoglycemia
  • Time Frame: During pregnancy
    Safety Issue?: Yes
• Failed metformin therapy
  • Time Frame: Duration of pregnancy
    Safety Issue?: No
• Cesarean section rate
  • Time Frame: At the time of delivery
    Safety Issue?: No
• Rate of macrosomia
  • Time Frame: At the time of delivery
    Safety Issue?: No
• Rate of shoulder dystocia
  • Time Frame: At the time of delivery
    Safety Issue?: No
• Respiratory distress syndrome of the newborn
  • Time Frame: Neonatal period
    Safety Issue?: No
• Need for neonatal dextrose
  • Time Frame: Neonatal period
    Safety Issue?: No

Inclusion Criteria:

• The onset of T2DM for less than 10 years prior to the onset of pregnancy by patient history
• Treatment with diet or oral hypoglycemic agents prior to pregnancy.
• Pregnancies less than 20 weeks of pregnancy. This gestational age was chosen to include those women who initiated prenatal care in the second trimester, but still have the ability to improve their hemoglobin A1C (primary outcome) with medical therapy prior to delivery.
• Newly diagnosed diabetes in the first 20 weeks of pregnancy. These women likely have had diabetes prior to the onset of pregnancy. They do not qualify for the diagnosis of gestational diabetes which is typically made after 20 weeks of pregnancy.
• Diagnosis will be made based on an elevated fasting blood glucose greater than 105 mg/dL, a 50 gram glucola result greater than 200 mg/dL or an abnormal 3 hour glucola test prior to 20 weeks of pregnancy. An abnormal 3-hour glucola test is defined as 2 out of 4 abnormal values.
• Hemoglobin A1C <9%

Exclusion Criteria:

• Gestational age greater than 20 weeks
• Multiple gestations (twins or more gestations)
• Type 1 diabetes by patient history
• Known fetal chromosomal or structural defects
• Contraindications to the use of metformin including renal disease, liver disease, prior myocardial infarction or sepsis.
• Those with a hemoglobin A1C greater than 9%.
• On insulin at the start of pregnancy

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 52 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: The University of Texas Health Science Center, Houston Other

Overall Clinical Trial Officials and Contacts

Jerrie S Refuerzo, M.D. Principal Investigator The University of Texas Health Science Center, Houston  

Overall Contact: Jerrie S Refuerzo, M.D. 713-500-6416 Jerrie.S.Refuerzo@uth.tmc.edu

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00678080

Study ID Number: HSC-MS-08-0015

ClinicalTrials.gov Identifier: NCT00678080

Health Authority: United States: Institutional Review Board