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Comparison of Insulin Alone to Insulin With Metformin to Treat Gestational Diabetes Mellitus

Phase 3
Terminated
Conditions
Gestational Diabetes
Interventions
Drug: Insulin
Drug: Metformin
Registration Number
NCT03651531
Lead Sponsor
Women and Infants Hospital of Rhode Island
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
Female
Target Recruitment
1
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.
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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
insulinInsulin-
insulin and metforminInsulin-
insulin and metforminMetformin-
Primary Outcome Measures
NameTimeMethod
Hgb A1ccollected at the time of delivery

Hgb A1c test

Secondary Outcome Measures
NameTimeMethod
Change in hemoglobin A1c over the course of the pregnancyhemoglobin 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 effectsWill be assessed weekly until delivery

maternal reported medication side effects (i.e. nausea, vomiting, diarrhea)

Treatment acceptabilityWill 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

Incidence of hypertensive disorder of pregnancyfrom enrollment through study completion (30 days after delivery)

gestational HTN, superimposed pre-eclampsia, pre-eclampsia-eclampsia

Incidence of composite of adverse maternal outcomesfrom enrollment through study completion (30 days after delivery)

death, ICU admission, postpartum hemorrhage, blood transfusion, organ failure, chorioamnionitis/endometritis

Breast feeding statusWill 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 deliveryrecorded at time of delivery

Mode of delivery

Gestational age at deliveryrecorded 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)

Total daily dose of insulinWill be recorded on hospital admission for delivery

Total daily dose of insulin at the end of pregnancy

Maternal weight gainThis 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

Glucose controlpatients 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 hypoglycemiapatients will be screened weekly for episodes of hypoglycemia until delivery

episodes of maternal hypoglycemia defined as glucose ≤70 mg/dL

Incidence of composite neonatal morbidityfrom 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 neonatal hypoglycemiafrom delivery through study completion (30 days after delivery)

hypoglycemia requiring intravenous treatment

Trial Locations

Locations (1)

Women & Infants Hospital

🇺🇸

Providence, Rhode Island, United States

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