Type 2 diabetes mellitus Nutritional, Metabolic, Endocrine Non-insulin-dependent diabetes mellitus
Conditions
Interventions
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
Sponsors
The Centre for Mother, Infant, and Child Research (CMICR) (Canada)
Eligibility
Sex/Gender
Female
Inclusion criteria
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
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 s | — |
Countries
Canada
Outcome results
None listed