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

This study has been completed.
Sponsor:
Collaborator:
WakeMed Health and Hospitals
Information provided by (Responsible Party):
Ashley Hickman, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT00835861
First received: February 2, 2009
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Non Insulin Dependent Diabetes
Pregnancy
Drug: Metformin
Drug: Insulin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of Metformin vs. Insulin in Pregnant Overt Diabetics (MIPOD)

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Blood Glucose Measurements [ Time Frame: Daily fasting and 1-hr post prandial measures were taken from time of enrollment until delivery ] [ Designated as safety issue: No ]
    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:
  • Number of Patients With Obstetric Complications [ Time Frame: Throughout pregnancy until hospital discharge following delivery. ] [ Designated as safety issue: No ]
    Maternal complications were stillbirths, major malformations, shoulder dystocia, or postpartum hemorrhage requiring transfusion.

  • Maternal Weight Gain [ Time Frame: Baseline throughout pregnancy until last prenatal visit. ] [ Designated as safety issue: No ]
  • Number of Babies With Neonatal Hypoglycemia [ Time Frame: Time of delivery through hospital discharge ] [ Designated as safety issue: No ]
    Initial neonatal glucose < 40 mg/dL

  • Glycosylated Hemoglobin (HbA1c) by Pregnancy Trimester [ Time Frame: 1st, 2nd, and 3rd trimester ] [ Designated as safety issue: No ]
  • Percent of Glucose Values at or Below Fasting Goal (<95 mg/dL) [ Time Frame: Baseline throughout pregnancy until time of delivery ] [ Designated as safety issue: No ]
    NUMBER OF ASSESSMENTS OF FASTING GLUCOSE VALUES <95

  • Percent of Glucose Values at or Below Postprandial Goal (<130 mg/dL) [ Time Frame: Baseline throughout pregnancy until time of delivery ] [ Designated as safety issue: No ]
    NUMBER OF ASSESSMENTS OF POSTPRANDIAL GLUCOSE VALUES <130

  • Number of Episodes Maternal Hypoglycemia [ Time Frame: Baseline throughout pregnancy until time of delivery ] [ Designated as safety issue: No ]
    Maternal glucose < 60 mg/dL

  • Number of Babies With Adverse Neonatal Outcomes [ Time Frame: Delivery until hospital discharge ] [ Designated as safety issue: No ]
    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.


Enrollment: 31
Study Start Date: August 2008
Study Completion Date: April 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Metformin
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.
Other Name: Glucophage
Active Comparator: 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.
Drug: Insulin
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.
Other Names:
  • Regular Insulin
  • Novolin R
  • Humulin R
  • NPH Insulin
  • Novolin N
  • Humulin N

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00835861

Locations
United States, North Carolina
University of North Carolina Hospitals Obstetric Clinics
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
WakeMed Health and Hospitals
Investigators
Principal Investigator: Ashley Hickman, MD University of North Carolina, Chapel Hill
  More Information

No publications provided by University of North Carolina, Chapel Hill

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ashley Hickman, MD, Clinical Instructor/Fellow, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00835861     History of Changes
Other Study ID Numbers: UNC08-0898
Study First Received: February 2, 2009
Results First Received: August 14, 2013
Last Updated: April 24, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by University of North Carolina, Chapel Hill:
Non Insulin Dependent Diabetes
Pregnancy

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Insulin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014