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

NCT00835861 | Completed Phase 2 Results

• 1 other identifier: UNC08-0898
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Non Insulin Dependent Diabetes; Pregnancy

Keywords

Non Insulin Dependent Diabetes; Pregnancy

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (8)

• Number of Patients With Obstetric Complications

  Throughout pregnancy until hospital discharge following delivery.

• Maternal Weight Gain

  Baseline throughout pregnancy until last prenatal visit.

• Number of Babies With Neonatal Hypoglycemia

  Time of delivery through hospital discharge

• Glycosylated Hemoglobin (HbA1c) by Pregnancy Trimester

  1st, 2nd, and 3rd trimester

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

  Baseline throughout pregnancy until time of delivery

Study Arms (2)

Metformin

EXPERIMENTAL

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

Insulin

ACTIVE COMPARATOR

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

Interventions

Metformin DRUG

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.

Also known as: Glucophage

Metformin

Insulin DRUG

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.

Also known as: Regular Insulin, Novolin R, Humulin R, NPH Insulin, Novolin N, Humulin N

Insulin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• WakeMed Health and Hospitals: collaborator

Study Sites (1)

University of North Carolina Hospitals Obstetric Clinics

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (1)

• Hickman MA, McBride R, Boggess KA, Strauss R. Metformin compared with insulin in the treatment of pregnant women with overt diabetes: a randomized controlled trial. Am J Perinatol. 2013 Jun;30(6):483-90. doi: 10.1055/s-0032-1326994. Epub 2012 Oct 24.

  PMID: 23096052 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Metformin; Insulin; Insulin, Isophane; Isophane Insulin, Human

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Insulin, Long-Acting; Insulin, Regular, Human

Limitations and Caveats

Unable to achieve enrollment goal before funding period expired because recruitment progressed more slowly than anticipated.

Results Point of Contact

• Title: M. Ashley Hickman Zink
• Organization: Maternal-Fetal Medicine and Obstetrics at UT Southwestern

m.ashley.hickman@gmail.com

469-303-3591

Study Officials

• Ashley Hickman, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2009
• First Posted: February 4, 2009
• Study Start: August 1, 2008
• Primary Completion: February 1, 2010
• Study Completion: April 1, 2010
• Last Updated: April 25, 2017
• Results First Posted: May 26, 2014

Record last verified: 2014-04

Locations

US (1)