Gestational Diabetes
Conditions
Keywords
metformin
Brief summary
This study is a prospective, unmasked randomized clinical trial comparing the use of insulin vs combination insulin and metformin for treatment in women diagnosed with gestational diabetes mellitus (GDM). The investigator's hypothesis is that the combination of metformin and insulin will be superior to insulin alone to achieve tight glucose control during pregnancy.
Detailed description
The objective of this study is to compare the effectiveness of insulin alone vs the combination of insulin and metformin in treating patients with gestational diabetes (GDM). Currently, outside of pregnancy, the treatment of type 2 diabetes mellitus (T2DM) with both metformin and insulin is superior to using insulin alone. In pregnancy, insulin alone has traditionally been used, though some advocate the use of metformin alone as primary therapy. There have been no trials published to date specifically comparing combination therapy to insulin alone. Our hypothesis is that the combination of metformin and insulin will improve overall control of blood glucose, the improvement of which has been demonstrated to improve maternal and neonatal outcomes. Control of blood glucose will be determined by hemoglobin A1c at the time of delivery.
Interventions
DRUGInsulin
Weight based insulin will be calculated using 0.7 units/kg/day in the first trimester, 0.8 units/kg/day in the second trimester and 1 units/kg/day in the third trimester. This total insulin will then be divided into short acting insulin and intermediate acting insulin per provider discretion.
DRUGMetformin
Will be initiated at dose of 500 mg twice daily. If glycemic control is suboptimal, the dose of metformin will be increased to 1000 mg twice a day. Metformin will be titrated prior to increases in insulin.
Sponsors
Women and Infants Hospital of Rhode Island
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Able to read and write English and/or Spanish and give written consent * Diagnosis of GDM, defined as an abnormal glucose tolerance test performed after 12 weeks gestation using 1 of the 2 criteria below: * 50 gram 1 hour oral diabetes screening testing yielding a result of \> 200 mg/dL * A 100 gram 3 hour oral glucose tolerance testing yielding \>2 abnormal values (normal values defined as fasting blood glucose \< 95, 1 hour \< 180, 2 hour \< 155 and 3 hour \< 140) * Singleton gestation * Gestational age between 12 and 34 weeks and 6 days determined by last menstrual period (LMP) confirmed by ultrasound using criteria set forth by the ACOG (Committee on Obstetric Practice). If LMP is unknown then gestational age must be set by ultrasound prior to 20 weeks gestation.
Exclusion criteria
* Pre-existing DM either by diagnosis preceding pregnancy or hemoglobin A1c \>6.5 collected during the current pregnancy * Uncontrolled chronic hypertension, as this may alter maternal and perinatal outcomes measured. * Multiple gestations * Major fetal anomalies anticipated to require NICU admission * Contraindication to metformin (allergy, history of lactic acidosis, pre-existing renal disease (Cr \>1.5 mg/dL), active liver disease, current alcohol abuse). * Vitamin B12 deficiency, as metformin reduces intestinal absorption of vitamin B12 * Medications known to effect glucose metabolism other than insulin and metformin as this may mask any effect between the two treatments. * Known inability to tolerate metformin.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hgb A1c | collected at the time of delivery | Hgb A1c test |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total daily dose of insulin | Will be recorded on hospital admission for delivery | Total daily dose of insulin at the end of pregnancy |
| Glucose control | patients will collect glucose values fasting and 2 hrs postprandial every day from enrollment until delivery. | Average of fasting and 2 hour postprandial glucose values |
| Incidence of maternal hypoglycemia | patients will be screened weekly for episodes of hypoglycemia until delivery | episodes of maternal hypoglycemia defined as glucose ≤70 mg/dL |
| Change in hemoglobin A1c over the course of the pregnancy | hemoglobin A1c will be collected at delivery (per above) and comparison performed after collection | If baseline hemoglobin A1c was collected as part of routine care prior to enrollment, this value will be compared to the hemoglobin A1c collected at delivery |
| Incidence of maternal side effects | Will be assessed weekly until delivery | maternal reported medication side effects (i.e. nausea, vomiting, diarrhea) |
| Treatment acceptability | Will be collected postpartum after delivery | determined using Diabetes Treatment Satisfaction Questionnaire. Survey includes 8 questions that are answered on a scale of 0-6; 0 indicating the least and 6 the highest level of satisfaction. The individual questions will be compared. Total satisfaction will also be compared by summing the responses to all 8 questions on a composite scale of 0-48 |
| Maternal weight gain | This will be calculated as the difference from the weight measured at the inital prenatal visit (the specific timing of which is patient dependant) and at the time of admission for delivery | weight gain through pregnancy |
| Incidence neonatal hypoglycemia | from delivery through study completion (30 days after delivery) | hypoglycemia requiring intravenous treatment |
| Incidence of composite of adverse maternal outcomes | from enrollment through study completion (30 days after delivery) | death, ICU admission, postpartum hemorrhage, blood transfusion, organ failure, chorioamnionitis/endometritis |
| Breast feeding status | Will be recorded at the time of hospital discharge after delivery (typically 2-4 days after delivery) | Whether patient is breast feeding or bottle feeding upon discharge from the hospital after delivery |
| Mode of delivery | recorded at time of delivery | Mode of delivery |
| Gestational age at delivery | recorded at time of delivery | Gestational age at delivery |
| Infant birthweight (using age/sex matched percentiles) | measured at time of birth | Infant birthweight (using age/sex matched percentiles) |
| Incidence of composite neonatal morbidity | from delivery through study completion (30 days after delivery) | Presence of any of the following: NICU admission, hypoglycemia, hyperbilirubinemia, birth trauma, stillbirth, respiratory distress syndrome, sepsis, neonatal death prior to discharge, 5 minute Apgar score \< 7, umbilical artery cord pH \<7.10 |
| Incidence of hypertensive disorder of pregnancy | from enrollment through study completion (30 days after delivery) | gestational HTN, superimposed pre-eclampsia, pre-eclampsia-eclampsia |
Countries
United States
Outcome results
None listed