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

ISRCTN	ISRCTN00928792
DOI	https://doi.org/10.1186/ISRCTN00928792
Protocol serial number	N/A
Sponsor	The Centre for Mother, Infant, and Child Research (CMICR) (Canada)
Funder	Canadian Institutes of Health Research (CIHR) (Canada)

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

Contact information

Dr Denice Feig
Scientific

C8-2075 Bayview Ave.
Toronto
M4N 3M5
Canada

Phone	+1 416 480 5631
Email	mity@sunnybrook.ca

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Metformin in Women with Type 2 Diabetes in Pregnancy a randomized controlled trial
Study acronym	MiTy
Study objectives	Among 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) studied	Type 2 diabetes mellitus
Intervention	Addition 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 type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Metformin, insulin
Primary outcome measure(s)	1. 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
Key secondary outcome measure(s)	1. 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
Completion date	31/12/2019

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	45 Years
Sex	Female
Target sample size at registration	500
Total final enrolment	502
Key inclusion criteria	1. 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 criteria	1. 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 enrolment	01/05/2011
Date of final enrolment	11/10/2018

Locations

Countries of recruitment

Canada

Study participating centre

C8-2075 Bayview Ave.

Toronto
M4N 3M5
Canada

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
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
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

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