Pregnancy Complications
Conditions
Keywords
Type 2 diabetes mellitus, Pregnancy, Metformin, Insulin, Pregnant women
Brief summary
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
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.
Interventions
DRUGMetformin
Metformin 500 mg orally daily increased as needed to maintain glycemic control until a maximum of 2500 daily
DRUGInsulin (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
Sponsors
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 52 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Who Achieved a Hemoglobin A1C <7% | during third trimester | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Hypoglycemia | During pregnancy | Defined as hypoglycemia as documented by neonatal chart based on health care provider description |
| Number of Participants Who Failed Metformin Therapy | Duration of pregnancy | Those whose glucose levels were above target range thereby needing insulin therapy |
| Number of Participants Who Had a Cesarean Section | At the time of delivery | — |
| Body Mass Index | 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 | — |
| Number of Participants With Fetus With Macrosomia | At the time of delivery | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Metformin Metformin therapy
Metformin: Metformin 500 mg orally daily increased as needed to maintain glycemic control until a maximum of 2500 daily | 8 |
| Insulin Insulin
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 | 13 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Metformin | Insulin | Total |
|---|---|---|---|
| Age, Continuous | 30.9 years STANDARD_DEVIATION 5.5 | 32.3 years STANDARD_DEVIATION 4.3 | 31.5 years STANDARD_DEVIATION 4.8 |
| Race/Ethnicity, Customized African American | 3 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Caucasian | 4 Participants | 6 Participants | 10 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment United States | 8 Participants | 13 Participants | 21 Participants |
| Sex: Female, Male Female | 8 Participants | 13 Participants | 21 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 0 / 13 |
| serious Total, serious adverse events | 0 / 8 | 0 / 13 |
Outcome results
Primary
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.
Time frame: during third trimester
Population: During the third trimester, hemoglobin A1c levels were obtained for only 5 in the metformin arm and 12 in the insulin arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metformin | The Number of Participants Who Achieved a Hemoglobin A1C <7% | 5 Participants |
| Insulin | The Number of Participants Who Achieved a Hemoglobin A1C <7% | 12 Participants |
Primary
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.
Time frame: at the time of delivery
Population: At the time of delivery, hemoglobin A1c levels were obtained for only 5 in the metformin arm and 8 in the insulin arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metformin | The Number of Participants Who Achieved a Hemoglobin A1C <7% | 5 Participants |
| Insulin | The Number of Participants Who Achieved a Hemoglobin A1C <7% | 7 Participants |
Secondary
Body Mass Index
Time frame: at the time of delivery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Body Mass Index | 35.9 kg/m^2 | Standard Deviation 5.2 |
| Insulin | Body Mass Index | 40.1 kg/m^2 | Standard Deviation 8.4 |
Secondary
Number of Participants Who Failed Metformin Therapy
Those whose glucose levels were above target range thereby needing insulin therapy
Time frame: Duration of pregnancy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metformin | Number of Participants Who Failed Metformin Therapy | 0 Participants |
Secondary
Number of Participants Who Had a Cesarean Section
Time frame: At the time of delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metformin | Number of Participants Who Had a Cesarean Section | 4 Participants |
| Insulin | Number of Participants Who Had a Cesarean Section | 6 Participants |
Secondary
Number of Participants Who Had a Newborn With Respiratory Distress Syndrome
Time frame: Neonatal period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metformin | Number of Participants Who Had a Newborn With Respiratory Distress Syndrome | 1 Participants |
| Insulin | Number of Participants Who Had a Newborn With Respiratory Distress Syndrome | 3 Participants |
Secondary
Number of Participants With Fetus With Macrosomia
Time frame: At the time of delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metformin | Number of Participants With Fetus With Macrosomia | 0 Participants |
| Insulin | Number of Participants With Fetus With Macrosomia | 1 Participants |
Secondary
Number of Participants With Hypoglycemia
Defined as hypoglycemia as documented by neonatal chart based on health care provider description
Time frame: During pregnancy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metformin | Number of Participants With Hypoglycemia | 0 Participants |
| Insulin | Number of Participants With Hypoglycemia | 0 Participants |
Secondary
Number of Participants With Newborns Who Needed Neonatal Dextrose
Time frame: Neonatal period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metformin | Number of Participants With Newborns Who Needed Neonatal Dextrose | 0 Participants |
| Insulin | Number of Participants With Newborns Who Needed Neonatal Dextrose | 1 Participants |
Secondary
Number of Participants With Shoulder Dystocia
Time frame: At the time of delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metformin | Number of Participants With Shoulder Dystocia | 1 Participants |
| Insulin | Number of Participants With Shoulder Dystocia | 0 Participants |