Metformin Versus Standard of Care Treatment in Pregnant Women With Prediabetes

Study Overview
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Brief Summary
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The purpose of this study is to assess if metformin reduces adverse outcomes associated with prediabetes in pregnancy. Our hypothesis is that pregnant women with prediabetes who are treated with metformin will show a greater reduction in large for gestational age infants at birth compared to women treated with the standard of care.

Detailed Description
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Women in pregnancy are routinely screened for diabetes in the first trimester and those who fall into the prediabetes category by hemoglobin A1c level of 5.7 to 6.4%, fasting plasma glucose of greater than or equal to 100 to 125, or oral glucose tolerance test of greater than or equal to 140 to less than 200 before 14 weeks gestation will be approached for consent in our randomized trial. Once consent is obtained, the subjects will be randomized 1:1 into two parallel groups, the metformin treatment group and the standard of care treatment group (routine prenatal care). A random number generator will allocate the participants to the study groups. Women taking metformin will continue twice daily dosing for the duration of their pregnancy after randomization. Those in the standard of care group will receive routine prenatal care. Both groups will undergo routine gestational diabetes testing by 28 weeks. Obstetric, maternal, and neonatal outcomes will then be assessed of both groups until the 6 week postpartum visit.

Official Title
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Metformin Versus Standard of Care Treatment in Pregnant Women With Prediabetes: A Randomized Trial

Conditions
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Prediabetes; Complicating Pregnancy

Intervention / Treatment
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* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women with hemoglobin A1c of 5.7 to 6.4%, fasting plasma glucose of greater than or equal to 100 to 125, or oral glucose tolerance test of greater than or equal to 140 to less than 200 before 14 weeks gestation Pregnancy and delivery care obtained at University of Massachusetts (UMass) Memorial Medical Center Patients able to provide written informed consent Exclusion Criteria: Pre-existing diabetes diagnosis as assessed at visit in the first trimester by history or by laboratory evaluation as listed above Presence of contra-indication to metformin (liver, renal, or heart failure) or sensitivity to metformin Participants who are under the age of 18 Multiple Pregnancy Patients already taking metformin for other indications Fetal defect noted on early dating ultrasound Miscarriage before randomization

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: This is a prospective, single center, randomized study evaluating metformin in the treatment of pregnant women with prediabetes on maternal and neonatal outcomes.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br>Study subjects will be randomized to the metformin medication arm. They will take a 500 mg tablet orally twice a day starting at 14 weeks of pregnancy until delivery. | Drug: Metformin<br>* Maximum dosage of 500 mg tablets 2 times a day (with each meal)<br>* Other names: Glucophage;|
| No Intervention: Standard of Care<br>Study subjects will be randomized to standard of care and receive routine prenatal care without further intervention for their prediabetes. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Birth Weight | Used to determine large for gestational age status | At Birth | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants needing Cesarean Section | Number of Participants with Cesarean Section | At Delivery | 
| Number of Participants with Postpartum Hemorrhage | Estimated or quantitative blood loss greater than 1000 mL | At Delivery | 
| Number of Participants with Development of Pregnancy Induced Hypertension | Blood pressure, serum laboratory analysis, and urine protein would be assessed for diagnosis | Through study completion, starting at 14 weeks until delivery | 
| Development of Gestational Diabetes | A glucose tolerance test would be conducted at 28 weeks of pregnancy to diagnose diabetes | Assessed at 28 weeks of pregnancy | 
| Maternal Weight Gain in Pregnancy |  | At enrollment and last prenatal visit, starting at 14 weeks until delivery | 
| Pregnancy Outcome | Number of Participants with Stillbirth, livebirth, pregnancy loss | Through study completion, starting at 14 weeks until delivery | 
| Number of Participants with Preterm birth | Less than 37 week delivery | At delivery | 
| Neonatal Intensive Care Unit Admission | Admission to level 2 or greater neonatal ICU and length of stay | At delivery and within first 2 days of life | 
| Apgar Score at Birth | <6 at 1 and 5 minutes | At delivery | 
| Number of Participants with Neonatal Birth Trauma | Brachial plexus injury | At Delivery | 
| Number of Participants with Shoulder Dystocia |  | At Delivery | 
| Number of Participants with Neonatal Hypoglycemia |  | Within first 2 days of life | 
| Number of Participants with Neonatal Respiratory Distress | Requiring 2 or more hours of respiratory support or oxygen with associated diagnosis | At Delivery | 
| Number of Participants with Neonatal Hyperbilirubinemia | Requiring phototherapy | Within first 2 days of life | 
| Number of Participants requiring Neonatal Intubation |  | At Delivery | 
| Neonatal Cooling | Need for neonatal cooling within first 48 hours of life | Within first 2 days of life | 
| Umbilical Cord Blood Level of C-peptide |  | At Birth | 
| Umbilical Cord Blood Level of Leptin |  | At Birth | 
| Umbilical Cord Blood Level of Insulin |  | At Birth | 
| Placental Pathology | Assessing for malperfusion pathology | At Birth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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maternal outcomes, neonatal outcomes, metformin, prediabetes, pregnancy