Medical Optimization of Management of Type 2 Diabetes Complicating Pregnancy (MOMPOD)

Study Overview
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Brief Summary
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Purpose: The objective of this proposal is to study the safety and efficacy of metformin added to insulin for treatment of type 2 diabetes mellitus (T2DM) among pregnant women. Participants: 950 pregnant women with type 2 diabetes complicating pregnancy from 10 U.S. clinical centers Procedures (methods): Pregnant women with T2DM between 10 weeks and 22 weeks 6 days and a singleton fetus will be randomized to double-blinded insulin/placebo versus insulin/metformin. Primary outcome is composite adverse neonatal outcome (clinically relevant hypoglycemia, birth trauma, hyperbilirubinemia, stillbirth/neonatal death). Study visits monthly at clinical visits; blood draw at 24-30 weeks, newborn anthropometric measurements at less than 72 hours of life. Maternal and infant outcomes will be chart abstracted.

Official Title
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Medical Optimization of Management of Type 2 Diabetes Complicating Pregnancy

Conditions
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Diabetes, Pregnancy

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Maternal age 18-45 years Singleton pregnancy with no known fetal anomalies Gestational age between 10weeks 0 days and 22 weeks 6 days by menstrual dating confirmed by ultrasound, or ultrasound alone Clinical diagnosis of preexisting T2DM requiring medical treatment (oral agent or insulin) Clinical diagnosis of diabetes diagnosed between 10 weeks and < 20 weeks 6 days gestation Willing to start insulin therapy and discontinue oral hypoglycemic pills other than study pills Able to swallow pills Exclusion Criteria: Clinical diagnosis of pre-existing renal disease, defined as creatinine > 1.5 mg/dL Clinical history of lactic acidosis Known allergy to metformin Participation in another study that could affect primary outcome Delivery planned at non-MOMPOD study locations Unwillingness to use insulin treatment or follow prenatal care doctor's instructions for insulin and blood glucose monitoring

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment<br>Metformin 1000 mg twice a day | Drug: Metformin<br>* 1000 mg twice a day<br>* Other names: Riomet;|
| Sham Comparator: Placebo<br>Placebo, identical to Metformin | Drug: Placebo<br>* Delivered to match active drug<br>* Other names: Sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Composite Adverse Neonatal Outcome | Participants with one or more of the following: capillary blood glucose level of < 30 mg/dL or capillary blood glucose requiring medical treatment, or Birth trauma (umbilical cord artery pH < 7.0 or shoulder dystocia with brachial plexus injury), or Hyperbilirubinemia requiring phototherapy, or Deliver < 37 weeks' gestation, or Miscarry, are stillborn, experience a neonatal demise, or Large for gestational age infant (birth weight > 90th percentile for gestational age), or Small for gestational age infant (birth weight < 10th percentile for gestational age) or low birth weight (< 2500 gm) | An average of 48 hours for term infants and 30 days for preterm infants | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Maternal Side Effects | Secondary outcome of maternal side effects were defined as: clinically relevant hypoglycemia defined as capillary blood glucose < 60 or < 80 with symptoms GI side effects defined as nausea, vomiting, diarrhea | Throughout study until delivery at 40 weeks gestation | 
| Mean Infant Fat Mass | Neonatal fat mass measured by skin-fold thickness (anthropometrics).The circumference of the upper limb is the circumference of the upper arm, and the circumference of the lower limb equals the mean of the circumferences measured at the midthigh and calf. The volume of the subcutaneous layer of fat covering each cylinder is estimated by multiplying the length times the circumference times the layer of fat estimated by the skinfold measures. The triceps skinfold measure is used as an estimate of the fat thickness of the limbs, and the subscapular skinfold measure approximates the fat thickness of the trunk. Total body fat is estimated by summing the volumes of fat covering each of the cylinders and multiplying by 0.9 (the density of fat). | Within 72 hrs of birth | 
| Maternal Safety Based on Treatment Emergent Adverse Events | Adverse maternal outcomes. | An average of 48 hours following delivery | 
| Neonatal Safety Based on Treatment Emergent Adverse Events | Adverse neonatal outcomes | up to 28 days of life | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metformin, Glucophage, Riomet, Glumetza, Fortamet, Glucophage XR