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

Phase 3

Terminated

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Treatment	Metformin	Metformin 1000 mg twice a day
Placebo	Placebo	Placebo, identical to Metformin

Primary Outcome Measures

Name	Time	Method
Number of Participants With Composite Adverse Neonatal Outcome	An average of 48 hours for term infants and 30 days for preterm infants	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)

Secondary Outcome Measures

Name	Time	Method
Mean Infant Fat Mass	Within 72 hrs of birth	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).
Neonatal Safety Based on Treatment Emergent Adverse Events	up to 28 days of life	Adverse neonatal outcomes
Number of Participants With Maternal Side Effects	Throughout study until delivery at 40 weeks gestation	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
Maternal Safety Based on Treatment Emergent Adverse Events	An average of 48 hours following delivery	Adverse maternal outcomes.

Locations (10): University of Mississippi
🇺🇸
Jackson, Mississippi, United States
University of California - San Diego
🇺🇸
San Diego, California, United States
Ohio State University
🇺🇸
Columbus, Ohio, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
University of North Carolina
🇺🇸
Chapel Hill, North Carolina, United States
University of Alabama
🇺🇸
Birmingham, Alabama, United States
Columbia University
🇺🇸
New York, New York, United States
University of Texas Medical Branch
🇺🇸
Galveston, Texas, United States
University of Texas - Houston
🇺🇸
Houston, Texas, United States
University of Utah
🇺🇸
Salt Lake City, Utah, United States