Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| WakeMed Health and Hospitals | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Many women come into pregnancy with diabetes that is controlled with either Metformin or diet control; however, the current standard of care for the treatment of preexisting diabetes in pregnancy is insulin. Metformin is widely used in the non-pregnant population for glycemic control, and has been used in pregnancy for other indications without adverse maternal or fetal outcomes. What remains unproven is the ability of Metformin to adequately control glucose in women during pregnancy.
Our goal is to randomize 100 women who enter pregnancy with diabetes that is controlled by either diet or an oral agent and women who are found to have an abnormal glucose challenge test at less than 20 weeks to either standard treatment with weight based Regular and neutral protamine Hagedorn (NPH) insulin or Metformin. Our hypothesis is that Metformin will provide glycemic control that is equivalent to insulin in these women.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metformin | Experimental | Women who enter pregnancy with a diagnosis of non insulin dependent/Type 2 Diabetes that is controlled with diet or an oral hypoglycemic agent, and women who demonstrate abnormal glucose tolerance prior to 20 weeks of gestation by abnormal 3 hour glucose challenge testing will be offered study participation. After informed consent, they will be randomized 1:1 to either the Metformin or Insulin group. |
|
| Insulin | Active Comparator | Women who enter pregnancy with a diagnosis of non insulin dependent/Type 2 Diabetes that is controlled with diet or an oral hypoglycemic agent, and women who demonstrate abnormal glucose tolerance prior to 20 weeks of gestation by abnormal 3 hour glucose challenge testing will be offered study participation. After informed consent, they will be randomized 1:1 to either the Metformin or Insulin group. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin | Drug | Women randomized to the Experimental arm will receive standard diet and glucose self-monitoring education. They will be initiated on Metformin 500 BID if they were medication naïve, or will be continued on their current dosage of Metformin if they were taking it prior to pregnancy. At each clinic visit fasting and one hour post prandial glucose values will be reviewed, and dosage will be titrated to a maximum of 2250mg/day to achieve target glycemic control. If glycemic control can not be achieved with Metformin as a single agent insulin will be added. |
| Measure | Description | Time Frame |
|---|---|---|
| Blood Glucose Measurements | Patients self monitored glucose measures throughout pregnancy to aid glycemic control. Fasting morning measures and postprandial measures were taken at 1 hour after breakfast, lunch, and dinner. | Daily fasting and 1-hr post prandial measures were taken from time of enrollment until delivery |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Obstetric Complications | Maternal complications were stillbirths, major malformations, shoulder dystocia, or postpartum hemorrhage requiring transfusion. | Throughout pregnancy until hospital discharge following delivery. |
| Maternal Weight Gain |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Ashley Hickman, MD | University of North Carolina, Chapel Hill | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of North Carolina Hospitals Obstetric Clinics | Chapel Hill | North Carolina | 27599 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23096052 | Derived | Hickman MA, McBride R, Boggess KA, Strauss R. Metformin compared with insulin in the treatment of pregnant women with overt diabetes: a randomized controlled trial. Am J Perinatol. 2013 Jun;30(6):483-90. doi: 10.1055/s-0032-1326994. Epub 2012 Oct 24. |
Not provided
Not provided
Not provided
Recruitment occurred at two hospitals from July 2008 through March 2010 at one and from January 2009 through December 2009 at the other.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Metformin | Patients received standard diet and glucose self-monitoring education. Medication naive patients were initiated on Metformin 500 BID or were continued on their current dosage of Metformin if taking prior to pregnancy. Self-reported glucose values were reviewed during each clinic visit and Metformin dosage was titrated up to a maximum of 2250 mg/day as needed for glycemic control. Insulin was added to those not achieving glycemic control with Metformin alone |
| FG001 | Insulin | Patients received standard diet and glycemic monitoring education. They were started on weight-based Regular and neutral protamine Hagedorn (NPH) insulin at a total dosage of 0.7units/kg in the first trimester or 0.8units/kg in the second trimester divided as 2/3 of the total dosage (with 2/3 given as NPH and 1/3 given as Regular) administered before breakfast and 1/3 of the total dosage (with 1/2 given as NPH and 1/2 given as Regular) administered with dinner. Self-reported glucose values were reviewed during each clinic visit and insulin dosage was titrated to achieve optimal glycemic control with fasting values <90 and one hour post prandial values <130. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Three women who never received the allocated treatment were excluded from the analysis.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Metformin | Patients received standard diet and glucose self-monitoring education. Medication naive patients were initiated on Metformin 500 BID or were continued on their current dosage of Metformin if taking prior to pregnancy. Self-reported glucose values were reviewed during each clinic visit and Metformin dosage was titrated up to a maximum of 2250 mg/day as needed for glycemic control. Insulin was added to those not achieving glycemic control with Metformin alone. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Blood Glucose Measurements | Patients self monitored glucose measures throughout pregnancy to aid glycemic control. Fasting morning measures and postprandial measures were taken at 1 hour after breakfast, lunch, and dinner. | For 1 infant in each group, the initial neonatal glucose value was missing. | Posted | Median | Inter-Quartile Range | mg/dL | Daily fasting and 1-hr post prandial measures were taken from time of enrollment until delivery |
|
From July 2008 through March 2010
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Metformin | Standard diet and glucose self-monitoring education. Initiated on Metformin 500 BID if medication naïve, or continued on their current dosage of Metformin if taking it prior to pregnancy. Dosage titrated to a maximum of 2250 mg/day based on review of self-reported fasting and post prandial glucose values during visits. .NPH Insulin treatment added for those unable to achieve glycemic control with Metformin alone. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Intrauterine fetal demise | Pregnancy, puerperium and perinatal conditions | Non-systematic Assessment | In the metformin group, one woman experienced a 13-week intrauterine fetal demise attributed to a large subchorionic hematoma noted on ultrasound at 12 weeks. |
Not provided
Unable to achieve enrollment goal before funding period expired because recruitment progressed more slowly than anticipated.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| M. Ashley Hickman Zink | Maternal-Fetal Medicine and Obstetrics at UT Southwestern | 469-303-3591 | m.ashley.hickman@gmail.com |
Not provided
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D008687 | Metformin |
| D007328 | Insulin |
| D007336 | Insulin, Isophane |
| D000068880 | Isophane Insulin, Human |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D011384 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Insulin | Drug | Women randomized to the Insulin group will receive standard diet and glycemic monitoring education. They will be initiated on weight based Regular and NPH insulin at a total dosage of 0.7units/kg in the first trimester or 0.8units/kg in the second trimester divided as 2/3 of the total dosage (with 2/3 given as NPH and 1/3 given as Regular) administered before breakfast and 1/3 of the total dosage (with 1/2 given as NPH and 1/2 given as Regular)administered with dinner. At each clinic visit fasting and one hour post prandial glucose values will be reviewed, and dosage will be titrated to achieve optimal glycemic control with fasting values <90 and one hour post prandial values <130. |
|
|
| Baseline throughout pregnancy until last prenatal visit. |
| Number of Babies With Neonatal Hypoglycemia | Initial neonatal glucose < 40 mg/dL | Time of delivery through hospital discharge |
| Glycosylated Hemoglobin (HbA1c) by Pregnancy Trimester | 1st, 2nd, and 3rd trimester |
| Percent of Glucose Values at or Below Fasting Goal (<95 mg/dL) | NUMBER OF ASSESSMENTS OF FASTING GLUCOSE VALUES <95 | Baseline throughout pregnancy until time of delivery |
| Percent of Glucose Values at or Below Postprandial Goal (<130 mg/dL) | NUMBER OF ASSESSMENTS OF POSTPRANDIAL GLUCOSE VALUES <130 | Baseline throughout pregnancy until time of delivery |
| Number of Episodes Maternal Hypoglycemia | Maternal glucose < 60 mg/dL | Baseline throughout pregnancy until time of delivery |
| Number of Babies With Adverse Neonatal Outcomes | Resuscitation in the delivery room, preterm birth < 37 weeks, neonatal intensive care unit care, birth injury or diagnosis of neonatal complication, glucose infusion, antibiotics, or phototherapy. | Delivery until hospital discharge |
| BG001 | Insulin | Patients received standard diet and glycemic monitoring education. They were started on weight-based Regular and NPH insulin at a total dosage of 0.7units/kg in the first trimester or 0.8units/kg in the second trimester divided as 2/3 of the total dosage (with 2/3 given as NPH and 1/3 given as Regular) administered before breakfast and 1/3 of the total dosage (with 1/2 given as NPH and 1/2 given as Regular) administered with dinner. Self-reported glucose values were reviewed during each clinic visit and insulin dosage was titrated to achieve optimal glycemic control with fasting values <90 and one hour post prandial values <130. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Insulin | Standard diet and glycemic monitoring education. Initiated on weight-based Regular and NPH insulin at a total dosage of 0.7units/kg in the first trimester or 0.8units/kg in the second trimester divided as 2/3 of the total dosage (with 2/3 given as NPH and 1/3 given as Regular) administered before breakfast and 1/3 of the total dosage (with 1/2 given as NPH and 1/2 given as Regular) administered with dinner. Dosage titrated during visits to achieve optimal glycemic control with fasting values <90 mg/dL and 1-hr post prandial values < 130 mg/dL. |
|
|
| Secondary | Number of Patients With Obstetric Complications | Maternal complications were stillbirths, major malformations, shoulder dystocia, or postpartum hemorrhage requiring transfusion. | Posted | Number | participants | Throughout pregnancy until hospital discharge following delivery. |
|
|
|
| Secondary | Maternal Weight Gain | Posted | Median | Inter-Quartile Range | kg/week | Baseline throughout pregnancy until last prenatal visit. |
|
|
|
| Secondary | Number of Babies With Neonatal Hypoglycemia | Initial neonatal glucose < 40 mg/dL | For 1 infant in each group, the initial neonatal glucose value was missing. | Posted | Number | Number of babies | Time of delivery through hospital discharge |
|
|
|
| Secondary | Glycosylated Hemoglobin (HbA1c) by Pregnancy Trimester | Posted | Median | Inter-Quartile Range | percentage of glycosolated hemoglobin | 1st, 2nd, and 3rd trimester |
|
|
|
| Secondary | Percent of Glucose Values at or Below Fasting Goal (<95 mg/dL) | NUMBER OF ASSESSMENTS OF FASTING GLUCOSE VALUES <95 | Posted | Number | percent of glucose values | Baseline throughout pregnancy until time of delivery |
|
|
|
| Secondary | Percent of Glucose Values at or Below Postprandial Goal (<130 mg/dL) | NUMBER OF ASSESSMENTS OF POSTPRANDIAL GLUCOSE VALUES <130 | Posted | Number | percent of glucose values | Baseline throughout pregnancy until time of delivery |
|
|
|
| Secondary | Number of Episodes Maternal Hypoglycemia | Maternal glucose < 60 mg/dL | Posted | Number | Number of episodes | Baseline throughout pregnancy until time of delivery |
|
|
|
| Secondary | Number of Babies With Adverse Neonatal Outcomes | Resuscitation in the delivery room, preterm birth < 37 weeks, neonatal intensive care unit care, birth injury or diagnosis of neonatal complication, glucose infusion, antibiotics, or phototherapy. | For 1 infant in the metformin group, the "adverse neonatal outcome" data was missing. | Posted | Number | number of babies | Delivery until hospital discharge |
|
|
|
| 1 |
| 14 |
| 0 |
| 14 |
| EG001 | Insulin | Standard diet and glycemic monitoring education. Initiated on weight-based Regular and NPH insulin at a total dosage of 0.7units/kg in the first trimester or 0.8units/kg in the second trimester divided as 2/3 of the total dosage (with 2/3 given as NPH and 1/3 given as Regular) administered before breakfast and 1/3 of the total dosage (with 1/2 given as NPH and 1/2 given as Regular) administered with dinner. Dosage titrated during visits to achieve optimal glycemic control with fasting values <90 mg/dL and 1-hr post prandial values < 130 mg/dL. | 0 | 14 | 0 | 14 |
|
Not provided
Not provided
| D004700 | Endocrine System Diseases |
| Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D049528 | Insulin, Long-Acting |
| D061386 | Insulin, Regular, Human |
| 3rd trimester |
|
| 28-30 weeks; n=253, 201 |
|
| 36-38 weeks; n=115, 83 |
|
| 28-30 weeks; n=652, 559 |
|
| 36-38 weeks; n=272,228 |
|