A Comparison Between Two Oral Hypoglycemics - Metformin and Glybenclamide for the Treatment of Gestational Diabetes Mellitus

Overview[ - collapse ][ - ]

Purpose Rationale Gestational diabetes mellitus (GDM) complicates 5-7% of pregnancies. Major hazards include macrosomia, polyhydramnios, labor trauma and neonatal hypoglycemia. The ADA and ACOG recommend glucose control in order to reduce the incidence of hyperglycemia induced complications. Glucose control can be achieved using diet and life style changes. Insulin is initiated in women who fail to obtain glucose control with diet alone. During the past 11 years oral hypoglycemic drugs have been tested and proven to be efficacious and safe. Objectives 1. To compare the efficacy and safety of glybenclamide vs. metformin in the treatment of women diagnosed with GDM 2. To evaluate the improvement in glycemic control after the addition of a second oral hypoglycemic drug after failure of the first Hypothesis GDM is one of the major conditions contributing to obstetrical complications and prenatal morbidity. Improving glycemic control, by means of improving compliance and patient satisfaction, will decrease obstetrical complications, maternal and neonatal morbidity and have positive long term health implications. Study design Prospective, randomized, open label Study population Women between the ages 18-45, diagnosed with GDM will be recruited. GDM will be defined by a pathological OGTT (according to Carpenter and Coustan criteria) performed at or after 13 weeks of gestation. Study period From recruitment until discharge of the newborn baby after delivery Power analysis Assuming 80% glycemic control with glybenclamide vs 55% with metformin, 52 women will be needed in each group in order to detect 25% difference in glycemic control rate with α=0.05 and β=0.2. Study protocol Women will be randomized at recruitment. Demographic and obstetrical data will be collected. Average glucose levels during the previous two weeks, estimated fetal weight and amniotic fluid index, and lab exams reflecting glycemic control will be noted. Women will provide daily glucose levels via fax or mail once a week. Glycemic control will be evaluated by a daily chart, including 7 measurements: 3 preprandial, 3 postprandial and a 7th measurement at 10 pm. Women will be invited to a monthly follow-up, which will include a sonographic evaluation of fetal weight and amniotic fluid, and lab exams. Follow-up protocol after 38 w of gestation will be according to our ward's protocol. The study was approved by the local Helsinki committee. Time table Duration: two years
ConditionGestational Diabetes Mellitus
InterventionDrug: metformin
Drug: glybenclamide
PhasePhase 4
SponsorHaEmek Medical Center, Israel
Responsible PartyHaEmek Medical Center, Israel
ClinicalTrials.gov IdentifierNCT01563120
First ReceivedDecember 28, 2011
Last UpdatedMarch 23, 2012
Last verifiedMarch 2012

Tracking Information[ + expand ][ + ]

First Received DateDecember 28, 2011
Last Updated DateMarch 23, 2012
Start DateJanuary 2012
Estimated Primary Completion DateJanuary 2014
Current Primary Outcome Measuresglycemic control [Time Frame: 2 years] [Designated as safety issue: No]
Current Secondary Outcome MeasuresNot Provided

Descriptive Information[ + expand ][ + ]

Brief TitleA Comparison Between Two Oral Hypoglycemics - Metformin and Glybenclamide for the Treatment of Gestational Diabetes Mellitus
Official TitleNot Provided
Brief Summary
Rationale Gestational diabetes mellitus (GDM) complicates 5-7% of pregnancies. Major hazards
include macrosomia, polyhydramnios, labor trauma and neonatal hypoglycemia. The ADA and ACOG
recommend glucose control in order to reduce the incidence of hyperglycemia induced
complications. Glucose control can be achieved using diet and life style changes. Insulin is
initiated in women who fail to obtain glucose control with diet alone. During the past 11
years oral hypoglycemic drugs have been tested and proven to be efficacious and safe.

Objectives

1. To compare the efficacy and safety of glybenclamide vs. metformin in the treatment of
women diagnosed with GDM

2. To evaluate the improvement in glycemic control after the addition of a second oral
hypoglycemic drug after failure of the first

Hypothesis GDM is one of the major conditions contributing to obstetrical complications and
prenatal morbidity. Improving glycemic control, by means of improving compliance and patient
satisfaction, will decrease obstetrical complications, maternal and neonatal morbidity and
have positive long term health implications.

Study design Prospective, randomized, open label

Study population Women between the ages 18-45, diagnosed with GDM will be recruited. GDM
will be defined by a pathological OGTT (according to Carpenter and Coustan criteria)
performed at or after 13 weeks of gestation.

Study period From recruitment until discharge of the newborn baby after delivery

Power analysis Assuming 80% glycemic control with glybenclamide vs 55% with metformin, 52
women will be needed in each group in order to detect 25% difference in glycemic control
rate with α=0.05 and β=0.2.

Study protocol Women will be randomized at recruitment. Demographic and obstetrical data
will be collected. Average glucose levels during the previous two weeks, estimated fetal
weight and amniotic fluid index, and lab exams reflecting glycemic control will be noted.
Women will provide daily glucose levels via fax or mail once a week. Glycemic control will
be evaluated by a daily chart, including 7 measurements: 3 preprandial, 3 postprandial and a
7th measurement at 10 pm. Women will be invited to a monthly follow-up, which will include
a sonographic evaluation of fetal weight and amniotic fluid, and lab exams. Follow-up
protocol after 38 w of gestation will be according to our ward's protocol. The study was
approved by the local Helsinki committee.

Time table Duration: two years
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionGestational Diabetes Mellitus
InterventionDrug: metformin
metformin up to 2550mg per day.
Drug: glybenclamide
glybenclamide up to 20mg per day.
Study Arm (s)
  • Active Comparator: metformin
    metformin up to 2550mg per day
  • Active Comparator: glybenclamide
    glybenclamide up to 20mg per day.

Recruitment Information[ + expand ][ + ]

Recruitment StatusEnrolling by invitation
Estimated Enrollment104
Estimated Completion DateJanuary 2014
Estimated Primary Completion DateJanuary 2014
Eligibility Criteria
Inclusion Criteria:

1. Patients with GDM with a gestational age between 14-33 weeks

2. Fasting glucose over 95 mg% or over 130 mg% an hour and a half postprandial (PPD) or
a daily average over 100 mg%

3. At least a week of dietary treatment

4. Sonographic dating of the pregnancy earlier than 24 weeks

5. Signing a consent form

Exclusion Criteria:

1. Suspected IUGR earlier than 24 week of gestation

2. Major fetal malformation

3. Pre-gestational diabetes mellitus
GenderFemale
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesIsrael

Administrative Information[ + expand ][ + ]

NCT Number NCT01563120
Other Study ID Numbers0002-11-EMC
Has Data Monitoring CommitteeNot Provided
Information Provided ByHaEmek Medical Center, Israel
Study SponsorHaEmek Medical Center, Israel
CollaboratorsNot Provided
Investigators Not Provided
Verification DateMarch 2012

Locations[ + expand ][ + ]

Dep. OB/GYN, Emek Medical Center
Afula, Israel