Effectiveness of Metformin Compared to Insulin in Pregnant Women With Mild Preexisting or Early Gestational Diabetes

Phase 2

Completed

Brief Summary: Many women come into pregnancy with diabetes that is controlled with either Metformin or diet control; however, the current standard of care for the treatment of preexisting diabetes in pregnancy is insulin. Metformin is widely used in the non-pregnant population for glycemic control, and has been used in pregnancy for other indications without adverse maternal or fetal outcomes. What remains unproven is the ability of Metformin to adequately control glucose in women during pregnancy.

Our goal is to randomize 100 women who enter pregnancy with diabetes that is controlled by either diet or an oral agent and women who are found to have an abnormal glucose challenge test at less than 20 weeks to either standard treatment with weight based Regular and neutral protamine Hagedorn (NPH) insulin or Metformin. Our hypothesis is that Metformin will provide glycemic control that is equivalent to insulin in these women.

Recruitment & Eligibility

Inclusion Criteria

Receiving prenatal care at University of North Carolina (UNC), Chapel Hill Obstetric clinics and planning delivery at UNC Women's Hospital
Diagnosis of Diabetes prior to pregnancy with use of an oral hypoglycemic agent or dietary control
Diagnosis of early gestational diabetes prior to 20 weeks gestation via abnormal 3 hour glucose challenge testing using the national diabetes data group (NDDG)criteria
Less than 24 weeks at study enrollment
Singleton or twin pregnancy
English or Spanish speaking
Able to give informed consent

Exclusion Criteria

End organ complications of diabetes (retinopathy, renal insufficiency, etc.)
Prior need for insulin for glycemic control
History of diabetic ketoacidosis (DKA) or hyperosmolar state
Prior adverse reaction (ie. lactic acidosis) or allergy to Metformin
Kidney or liver disease
Significant medical co-morbidities (lupus, cystic fibrosis, etc.) Hypertension controlled on one medication, well controlled asthma, and well controlled thyroid disease are not excluded.

Arm && Interventions

Group	Intervention	Description
Insulin	Insulin	Women who enter pregnancy with a diagnosis of non insulin dependent/Type 2 Diabetes that is controlled with diet or an oral hypoglycemic agent, and women who demonstrate abnormal glucose tolerance prior to 20 weeks of gestation by abnormal 3 hour glucose challenge testing will be offered study participation. After informed consent, they will be randomized 1:1 to either the Metformin or Insulin group.
Metformin	Metformin	Women who enter pregnancy with a diagnosis of non insulin dependent/Type 2 Diabetes that is controlled with diet or an oral hypoglycemic agent, and women who demonstrate abnormal glucose tolerance prior to 20 weeks of gestation by abnormal 3 hour glucose challenge testing will be offered study participation. After informed consent, they will be randomized 1:1 to either the Metformin or Insulin group.

Primary Outcome Measures

Name	Time	Method
Blood Glucose Measurements	Daily fasting and 1-hr post prandial measures were taken from time of enrollment until delivery	Patients self monitored glucose measures throughout pregnancy to aid glycemic control. Fasting morning measures and postprandial measures were taken at 1 hour after breakfast, lunch, and dinner.

Secondary Outcome Measures

Name	Time	Method
Number of Babies With Neonatal Hypoglycemia	Time of delivery through hospital discharge	Initial neonatal glucose \< 40 mg/dL
Percent of Glucose Values at or Below Fasting Goal (<95 mg/dL)	Baseline throughout pregnancy until time of delivery	NUMBER OF ASSESSMENTS OF FASTING GLUCOSE VALUES \<95
Number of Babies With Adverse Neonatal Outcomes	Delivery until hospital discharge	Resuscitation in the delivery room, preterm birth \< 37 weeks, neonatal intensive care unit care, birth injury or diagnosis of neonatal complication, glucose infusion, antibiotics, or phototherapy.
Number of Patients With Obstetric Complications	Throughout pregnancy until hospital discharge following delivery.	Maternal complications were stillbirths, major malformations, shoulder dystocia, or postpartum hemorrhage requiring transfusion.
Maternal Weight Gain	Baseline throughout pregnancy until last prenatal visit.
Glycosylated Hemoglobin (HbA1c) by Pregnancy Trimester	1st, 2nd, and 3rd trimester
Percent of Glucose Values at or Below Postprandial Goal (<130 mg/dL)	Baseline throughout pregnancy until time of delivery	NUMBER OF ASSESSMENTS OF POSTPRANDIAL GLUCOSE VALUES \<130
Number of Episodes Maternal Hypoglycemia	Baseline throughout pregnancy until time of delivery	Maternal glucose \< 60 mg/dL