Metformin Versus Insulin in Pregnant Women With Type 2 Diabetes

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pregnancy Complications

Intervention / Treatment
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* Drug: Metformin
* Drug: Insulin (NPH and Regular)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 52 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br>Metformin therapy as prescribed by their health care provider | Drug: Metformin<br>* Metformin 500 mg orally daily increased as needed to maintain glycemic control until a maximum of 2500 daily<br>* Other names: Glucophage;|
| Active Comparator: Insulin<br>Insulin as prescribed by their health care provider | Drug: Insulin (NPH and Regular)<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants Who Achieved a Hemoglobin A1C <7% | The hemoglobin A1c level is an indicator of glycemic control-it indicates the average level of blood sugar over the past 2 to 3 months. Hemoglobin A1c levels 6.5% and higher indicate diabetes. | during third trimester | 
| The Number of Participants Who Achieved a Hemoglobin A1C <7% | The hemoglobin A1c level is an indicator of glycemic control-it indicates the average level of blood sugar over the past 2 to 3 months. Hemoglobin A1c levels 6.5% and higher indicate diabetes. | at the time of delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Mass Index |  | at the time of delivery | 
| Number of Participants With Hypoglycemia | Defined as hypoglycemia as documented by neonatal chart based on health care provider description | During pregnancy | 
| Number of Participants Who Failed Metformin Therapy | Those whose glucose levels were above target range thereby needing insulin therapy | Duration of pregnancy | 
| Number of Participants Who Had a Cesarean Section |  | At the time of delivery | 
| Number of Participants With Fetus With Macrosomia |  | At the time of delivery | 
| Number of Participants With Shoulder Dystocia |  | At the time of delivery | 
| Number of Participants Who Had a Newborn With Respiratory Distress Syndrome |  | Neonatal period | 
| Number of Participants With Newborns Who Needed Neonatal Dextrose |  | Neonatal period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes mellitus, Pregnancy, Metformin, Insulin, Pregnant women