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

University of North Carolina, Chapel Hill31 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Non Insulin Dependent Diabetes Pregnancy

Interventions

MetforminDRUG

Women randomized to the Experimental arm will receive standard diet and glucose self-monitoring education. They will be initiated on Metformin 500 BID if they were medication naïve, or will be continued on their current dosage of Metformin if they were taking it prior to pregnancy. At each clinic visit fasting and one hour post prandial glucose values will be reviewed, and dosage will be titrated to a maximum of 2250mg/day to achieve target glycemic control. If glycemic control can not be achieved with Metformin as a single agent insulin will be added.

InsulinDRUG

Women randomized to the Insulin group will receive standard diet and glycemic monitoring education. They will be initiated on weight based Regular and NPH insulin at a total dosage of 0.7units/kg in the first trimester or 0.8units/kg in the second trimester divided as 2/3 of the total dosage (with 2/3 given as NPH and 1/3 given as Regular) administered before breakfast and 1/3 of the total dosage (with 1/2 given as NPH and 1/2 given as Regular)administered with dinner. At each clinic visit fasting and one hour post prandial glucose values will be reviewed, and dosage will be titrated to achieve optimal glycemic control with fasting values \<90 and one hour post prandial values \<130.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Blood Glucose Measurements

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.

Time frame: Daily fasting and 1-hr post prandial measures were taken from time of enrollment until delivery

Secondary Outcomes

Number of Patients With Obstetric Complications

Maternal complications were stillbirths, major malformations, shoulder dystocia, or postpartum hemorrhage requiring transfusion.

Time frame: Throughout pregnancy until hospital discharge following delivery.

Maternal Weight Gain

Time frame: Baseline throughout pregnancy until last prenatal visit.

Number of Babies With Neonatal Hypoglycemia

Initial neonatal glucose \< 40 mg/dL

Time frame: Time of delivery through hospital discharge

Glycosylated Hemoglobin (HbA1c) by Pregnancy Trimester

Time frame: 1st, 2nd, and 3rd trimester

Percent of Glucose Values at or Below Fasting Goal (<95 mg/dL)

NUMBER OF ASSESSMENTS OF FASTING GLUCOSE VALUES \<95

Time frame: Baseline throughout pregnancy until time of delivery

Percent of Glucose Values at or Below Postprandial Goal (<130 mg/dL)

NUMBER OF ASSESSMENTS OF POSTPRANDIAL GLUCOSE VALUES \<130

Time frame: Baseline throughout pregnancy until time of delivery

Number of Episodes Maternal Hypoglycemia

Maternal glucose \< 60 mg/dL

Time frame: Baseline throughout pregnancy until time of delivery

Number of Babies With Adverse Neonatal Outcomes

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.

Time frame: Delivery until hospital discharge

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes