Metformin Treatment in Gestational Diabetes and Noninsulin Dependent Diabetes in Pregnancy in a Developing Country

Overview[ - collapse ][ - ]

Purpose The study hypothesis was In women with gestational diabetes and type 2 diabetes in pregnancy metformin treatment compared with insulin will result in better perinatal and maternal outcome and improved treatment acceptability with low or noadditional insulin requirement.
ConditionGestational Diabetes
Type 2 Diabetes
Pregnancy
InterventionDrug: Metformin
Drug: Insulin
PhasePhase 2/Phase 3
SponsorDow University of Health Sciences
Responsible PartyDow University of Health Sciences
ClinicalTrials.gov IdentifierNCT01855763
First ReceivedMay 9, 2013
Last UpdatedMay 13, 2013
Last verifiedMay 2013

Tracking Information[ + expand ][ + ]

First Received DateMay 9, 2013
Last Updated DateMay 13, 2013
Start DateDecember 2008
Estimated Primary Completion DateDecember 2013
Current Primary Outcome Measures
  • Alive baby [Time Frame: At birth, up to 28 days after birth] [Designated as safety issue: Yes]it will include alive , neonatal death and still born
  • Neonatal morbidity [Time Frame: at birth upto 28 days after birth] [Designated as safety issue: Yes]it will include birth weight, macrosomia,neonatal hypoglycemia,transient tachypnoea of newborn ,respiratory distress syndrome,neonatal intensive care admissions, prematurity,sepsis,neonatal jaundice,birth trauma.
Current Secondary Outcome Measures
  • glycemic control [Time Frame: day1 (study entry ) till devlivery] [Designated as safety issue: Yes]fasting and random blood glucose levels , at study entry ,mean levels throughout pregnancy and at 36/37 weeks of pregnancy.
    HbA1 C Levels,at study entry and at 36/37 weeks of pregnancy
  • weight gain in prenancy [Time Frame: day 1 (study entry) till delivery] [Designated as safety issue: No]total weight gain in pregnancy in kg
  • Maternal hypertensive complications [Time Frame: day 1(study entry ) till 1 week after delivery] [Designated as safety issue: Yes]it will include pregnancy induced hypertension and preeclampsia.

Descriptive Information[ + expand ][ + ]

Brief TitleMetformin Treatment in Gestational Diabetes and Noninsulin Dependent Diabetes in Pregnancy in a Developing Country
Official TitleMetformin in Gestational Diabetes and type2 Diabetes in Pregnancy in a Developing Country
Brief Summary
The study hypothesis was In women with gestational diabetes and type 2 diabetes in pregnancy
metformin treatment compared with insulin will result in better perinatal and maternal
outcome and improved treatment acceptability with low or noadditional insulin requirement.
Detailed Description
METHODOLOGY:

This randomized clinical study comparing metformin and insulin in the treatment of
gestational diabetes and type 2 diabetes in pregnancy was conducted between December 2008
till December 2012 in the tertiary care university hospital of Lyari General Hospital and
Dow University of Health Sciences and in four other private obstetric (maternity) hospitals
of Karachi. The study was approved by the ethics committee of Dow University of Heath
Sciences. A written informed consent was taken from the participants of the study and the
consequences and suspected outcomes were informed.

The patients were selected from those attending the antenatal clinic with previously
diagnosed type 2 diabetes or were screened in antenatal clinic due to presence of high risk
factors for diabetes mellitus and were found to have impaired glucose tolerance (IGT) or
gestational diabetes mellitus (GDM).

All pregnant women were subjected to screening after evaluation of high risk factors at
their first antenatal visit irrespective of gestational age in order to pick undiagnosed
type 2 diabetes early in pregnancy. Women who were screen negative at first antenatal visit
were subjected to repeat screening at 24-28 weeks and 32-36 weeks.

A 50gm oral glucose challenge test (GCT) was done as an initial screening test irrespective
of the fasting status and a blood sugar level of 140gm/dl was considered as a positive GCT.
Gestational diabetes was then diagnosed by a 2 hour 75gm oral glucose tolerance test (OGTT)
after an over night fast of 10 hours. Diagnosis of GDM was made with at least two out of
three abnormal high plasma glucose levels in a 75gm OGTT FBS> 95, 1 hour ≥180 and 2 hour
≥155.

All women with type 2 diabetes mellitus and screen positive of gestational diabetes with
pregnancy beyond first trimester and having FBS >100mg/dl and 1 ½ hour postprandial glucose
of >126mg/dl were advised for dietary modifications and life style counseling including
exercise. Women with blood glucose levels being too high and those who do not maintain the
required blood glucose levels on diet and exercise were included in the study and randomized
for treatment with metformin or insulin along with diet and exercise advice. Randomization
was done as the patients were divided into two groups as they enter the study.

Group A: Patients with gestational diabetes. Group B: Patients with type 2 diabetes. Each
group was further subdivided into two sub groups. Group A1: Received metformin treatment.
Group A2: Received insulin treatment. Group B1: Received metformin treatment. Group B2:
Received insulin treatment. Odd numbers in each group were assigned for metformin treatment
and even numbers in each group for insulin treatment. Blinding of the treatment was not
possible because of the different routes of administration. Patients not fulfilling the
inclusion criteria and controlled on diet alone were excluded from the study.

All the women were provided with standard nutritional instructions for three meals and three
snacks daily. Adherence to the dietary regimen was evaluated and reinforced at weekly or
fortnightly antenatal visits. The diets were designed to provide 25kcal/kg of body weight
for non obese women with 40-45% calories from carbohydrates.

Metformin was started at dose of 500mg daily and increased up to 2500mg daily in divided
doses as tolerated by patient and depending on maternal glucose levels. Target blood glucose
values are taken as FBS of less than or equal to 100mg/dl (5.5 mmol/l) and RBS ≤ 126mg/dl
(7mmol/l). If blood glucose levels were higher than the cut off values after one to two
weeks of treatment and in spite of achieving the maximum dose of metformin, insulin was
added as supplementary treatment with metformin continued.

Insulin was added as supplementary treatment in patients not controlled with metformin alone
in 1-2 weeks or at any time when glycemic targets were not achieved with metformin alone.
Insulin was given as a combination of short acting and intermediate acting Human insulin
twice daily before meals. Patients were followed in outpatient clinic at 1-2 weeks interval
depending on blood glucose control till blood glucose levels were stabilized. However they
were provided the phone number to contact the researcher in case of any emergency or
otherwise.

Insulin was prescribed as a combination of short acting and intermediate acting human
insulin twice daily before meals. For estimation of starting dose of insulin a combination
of maternal weight in kg and pregnancy trimester was used. A 24-hour total insulin dose was
calculated using 0.7 units/kg in first trimester, 0.8 units/kg in second trimester and 0.9
units/kg in third trimester. Two thirds of the total dose was given in the morning before
breakfast and one third at night before dinner. Two thirds of the morning insulin dose was
given as intermediate acting insulin (Humulin N) and one third as short acting insulin
(Humulin R) with both given as single injection. Half of the night insulin is intermediate
acting and half was short acting insulin given in a single injection.
Study TypeInterventional
Study PhasePhase 2/Phase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • Gestational Diabetes
  • Type 2 Diabetes
  • Pregnancy
InterventionDrug: Metformin
Other Names:
  • GLUCOPHAGE
  • NEOPHAGE
Drug: Insulin
Other Names:
humulin insulin
Study Arm (s)
  • Experimental: metformin
    group A1:Consists of patients with GDM who were given drug metformin as treatment group B1:Consists of patients with type 2 diabetes in pregnancy were given the drug metformin as treatment intervention with drug metformin is given for control of diabetes in esclation dose of 500mg /day upto 2.5 grams per day in two to three divided doses till delivery
  • Active Comparator: insulin
    GroupA2:gestational diabetes on insulin treatment Group B2:type 2 diabetes on insulin treatment intervention:insulin treatment till delivery

Recruitment Information[ + expand ][ + ]

Recruitment StatusActive, not recruiting
Estimated Enrollment300
Estimated Completion DateDecember 2013
Estimated Primary Completion DateDecember 2013
Eligibility Criteria
Inclusion Criteria

1. Pregnancies in women with pre-pregnancy diagnosis of NIDDM (Type 2 DM) and pregnancy
continued beyond the first trimester.

2. Women with gestational diabetes mellitus who are at 20-34 weeks of gestation.

3. Women who have glucose elevations consistent with undiagnosed diabetes in pregnancy.

4. Women with impaired glucose tolerance (IGT) at any gestational age of pregnancy and
pregnancy continued beyond first trimester.

5. Singleton pregnancy.

Exclusion Criteria:

1. Women who have contraindication for metformin intake.

2. A recognized fetal anomaly at 14-16 weeks ultrasound examination at the time of study
entry.

3. Ruptured membranes at time of study entry.

4. Women with IDDM (Type 1 DM) entering pregnancy.

5. Presence of any other medical disorder like essential hypertension, renal disease,
hepatic disease, hypothyroidism, cardiac disease.

6. Presence of diabetic complications.

7. Patient already on Sulphonylureas.

8. Multiple pregnancy.

9. Gestational diabetes controlled on diet alone.

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GenderFemale
Ages20 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
ContactsNot Provided
Location CountriesNot Provided

Administrative Information[ + expand ][ + ]

NCT Number NCT01855763
Other Study ID Numbersmetformin in gdm & t 2 dm
Has Data Monitoring CommitteeYes
Information Provided ByDow University of Health Sciences
Study SponsorDow University of Health Sciences
CollaboratorsNot Provided
Investigators Principal Investigator: jahanara ainuddin, MBBS, FCPS Associate Professor Dow university of health sciences
Verification DateMay 2013