The effect of Metformin in women with Type 2 diabetes during pregnancy

ISRCTN ISRCTN00928792
DOI https://doi.org/10.1186/ISRCTN00928792
Secondary identifying numbers N/A
Submission date
21/03/2011
Registration date
26/07/2011
Last edited
29/01/2021
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Nutritional, Metabolic, Endocrine
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Study website

Contact information

Dr Denice Feig
Scientific

C8-2075 Bayview Ave.
Toronto
M4N 3M5
Canada

+1 416 480 5631
mity@sunnybrook.ca

Study information

Study designRandomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleMetformin in Women with Type 2 Diabetes in Pregnancy – a randomized controlled trial
Study acronymMiTy
Study objectivesAmong pregnant women with diagnosed type 2 diabetes mellitus, does the addition of metformin to a standard regimen of insulin increase or decrease the incidence of adverse perinatal outcomes as defined by a composite of: pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, and neonatal intensive care unit (NICU) admission > 24 hours, compared with women treated with insulin plus placebo?
Ethics approval(s)Mount Sinai Hospital Research Ethics Board approved on February 16, 2011; Ref :10-0129A
Health condition(s) or problem(s) studiedType 2 diabetes mellitus
InterventionAddition of metformin to a standard regimen of insulin among pregnant women with diagnosed type 2 diabetes mellitus compared with women treated with insulin plus placebo
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Metformin, insulin
Primary outcome measure1. Pregnancy loss
2. Preterm birth
3. Birth injury
4. Moderate/severe respiratory distress (RDS)
5. Neonatal hypoglycemia
6. Neonatal intensive care unit (NICU) admission > 24 hours
Secondary outcome measures1. Incidence of large for gestational age infants defined as greater than the 90th percentile for weight, based on the National Canadian fetal growth standards for singleton boys and girls
2. Pregnancy loss
3. Preterm birth (will record if spontaneous or indicated)
4. Birth injury
5. Respiratory distress
6. Neonatal hypoglycemia
7. NICU admission > 24 hours
8. Cord blood gases < 7.0
9. Elevated cord blood C-peptide
10. Fetal fat mass as measured by neonatal anthropometric measurements as measured by Catalano et al
11. Maternal glycemic control as measured by HbA1c and capillary glucose measurements. Gestational age at testing will be recorded. All downloaded glucose results will be transmitted on a regular basis to a central site for future analysis. Monthly correlations will be done with the laboratory during routine monthly blood draws.
12. Maternal hypoglycemia defined as mild (<3.6, symptomatic and asymptomatic or requiring treatment), or severe (loss of consciousness or confusion requiring assistance) will be documented at each visit
13. Maternal weight gain. The first and last weight will be obtained at the first and last visit in pregnancy, whether they be done by the endocrinologist, family physician or obstetrician. Consent from the mother will be obtained for this.
14. Maternal insulin doses (overall amount and number of patients that are taking high insulin doses defined as 2 units/kg or more per day)
15. Incidence of pre-eclampsia and/or gestational hypertension
16. Number of hospitalizations prior to admission for delivery and the duration of hospital stays for the mother prior to admission for delivery and associated with delivery
17. Rate of cesarean-section
18. Duration of hospital stay for infant associated with his/her birth until the first discharge home
Overall study start date01/05/2011
Completion date31/12/2019

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
Upper age limit45 Years
SexFemale
Target number of participants500
Total final enrolment502
Key inclusion criteria1. Women between the ages of 18-45
2. Women diagnosed with type 2 diabetes prior to pregnancy or women with undiagnosed type 2 diabetes diagnosed prior to 20 weeks gestation [defined as women presenting with gestational diabetes before 20 weeks gestation with an elevated glycosylated hemoglobin (HbA1c) which is 8% or more above the upper normal range (i.e. HbA1c of 6.5% if upper normal is 6.0%, or HbA1c 7% if upper normal is 6.5%) or fasting glucose >= 7.0 mmol/L]
3. Pregnancy gestation between 12 weeks 0 days - 22 weeks 6 days
4. Live singleton fetus
Key exclusion criteria1. Women who are not on insulin
2. Women who are on oral hypoglycemic agents should be switched to insulin prior to randomization
3. Diabetes diagnosed after 20 weeks gestation
4. Type 1 diabetes
5. Known intolerance to metformin
6. Contraindications to metformin use which include:
6.1 Renal insufficiency (defined as serum creatinine of greater than 130 umol/L or creatinine clearance < 60 ml/min
6.2 Moderate to severe liver dysfunction (defined as liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) greater than three times the upper limit of normal)
6.3 Shock or sepsis
6.4 Previous hypersensitivity to metformin
7. Women with significant gastrointestinal problems such as severe vomiting requiring intravenous fluids or hospitalization, or active Crohn's or colitis
8. Previous participation in the trial
9. Patients who have a fetus with a known potentially lethal anomaly will be excluded. Information regarding congenital anomalies diagnosed after randomization will be recorded.
10. Known higher order pregnancies (twins, triplets, etc). These women will be excluded as they have a higher rate of adverse outcomes and we want to avoid any inequalities if they are unequally distributed between the groups
11. Presence of acute or chronic metabolic acidosis, including diabetic ketoacidosis
12. History of diabetic ketoacidosis or history of lactic acidosis
13. Presence of excessive alcohol intake, acute or chronic
14. Presence of congestive heart failure or history of congestive heart failure
Date of first enrolment01/05/2011
Date of final enrolment11/10/2018

Locations

Countries of recruitment

  • Canada

Study participating centre

C8-2075 Bayview Ave.
Toronto
M4N 3M5
Canada

Sponsor information

The Centre for Mother, Infant, and Child Research (CMICR) (Canada)
Not defined

Sunnybrook Research Institute
C8-2075 Bayview Ave.
Toronto
M4N 3M5
Canada

+1 416 480 5631
mity@sunnybrook.ca
http://www.mity.ca/
ROR logo https://ror.org/03wefcv03

Funders

Funder type

Research organisation

Canadian Institutes of Health Research (CIHR) (Canada)
Government organisation / National government
Alternative name(s)
Instituts de Recherche en Santé du Canada, Canadian Institutes of Health Research (CIHR), CIHR_IRSC, Canadian Institutes of Health Research | Ottawa ON, CIHR, IRSC
Location
Canada

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/10/2020 29/01/2021 Yes No

Editorial Notes

29/01/2021: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
22/01/2019: The following changes have been made to the clinical trial record:
1. The recruitment end date has been changed from 01/12/2014 to 11/10/2018
2. The overall trial end date has been changed from 01/12/2014 to 31/12/2019

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