Clinical Trial: Metformin in Women With Type 2 Diabetes in Pregnancy Trial
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: Metformin in Women With Type 2 Diabetes in Pregnancy Trial
Brief Summary: Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, however despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes. The investigators hypothesize that metformin use, in addition to treatment with insulin, will help with blood sugar control, lower the dose of insulin needed, lower weight gain, and improve baby outcomes.
Detailed Summary: Type 2 diabetes in pregnancy is increasing in prevalence and these women continue to face increased rates of adverse maternal and fetal outcomes. The investigators hypothesize that metformin use, as an adjunct to insulin, will decrease these adverse outcomes by reducing maternal hyperglycemia, high maternal insulin doses, excessive maternal weight gain and gestational hypertension/pre-eclampsia, all of which should reduce perinatal and neonatal mortality and morbidity. In addition, since metformin crosses the placenta, metformin treatment of the fetus may have a direct beneficial effect on neonatal outcomes. This study is an randomized controlled trial (RCT) that adds metformin to insulin, and is a double-blind, placebo-controlled RCT. The investigators believe that neither metformin alone nor insulin alone will effectively treat this population, and therefore our design, which includes the addition of metformin to insulin, will be the most relevant to our patients.
Sponsor: Mount Sinai Hospital, Canada
Current Primary Outcome: A composite of: pregnancy loss, preterm birth, birth injury, moderate/severe respiratory distress, neonatal hypoglycemia, and NICU admission > 24 hours. [ Time Frame: conception to 28 days after birth ]
Original Primary Outcome: A composite of: pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, and NICU admission > 48 hours. [ Time Frame: conception to 28 days after birth ]
Current Secondary Outcome:
- Large for gestational age (LGA) infants [ Time Frame: Up to 24 hours after birth ]Defined as greater than the 90th percentile for weight, based on the National canadian fetal growth standards for singleton boys and girls.
- Pregnancy loss [ Time Frame: Up to 40 weeks gestation ]Spontaneous abortion defined as death of a fetus at <20 weeks gestation; Stillbirth defined as death of a fetus with a birth weight ≥ 500g or at ≥ 20 wks gestational age regardless of birth weight; Neonatal death defined as death of a live born infant within the first 28 days of life or prior to hospital discharge, whichever is later.
- Preterm birth [ Time Frame: Up to 37 weeks gestation ]Birth < 37 weeks gestation
- Respiratory distress [ Time Frame: within 72 hours after birth ]Given surfactant via an endotracheal tube and/or requiring assisted positive pressure ventilation within 72 hours after birth.
- Neonatal hypoglycemia [ Time Frame: NICU admission >24 hours ]A plasma glucose <2.6 mmol/L on one or more occasions, starting at 30-60 minutes after birth, and necessitating intravenous dextrose within the first 48 hours of life.
- NICU admission >24 hours [ Time Frame: NICU admission >24 hours ]Admission to a neonatal intensive or special care unit for > 24 hours during the initial hospitalization after birth
- Cord blood gases pH <7.0 [ Time Frame: Within 4 hours of birth ]
- Hyperinsulinemia as measured by elevated cord blood C-peptide [ Time Frame: Within 4 hours of birth ]A cord serum C-peptide value > 1.7 ug/L (which is >90th percentile of values for the total cohort of participants in the HAPO trial) will be defined as hyperinsulinemia.
- Maternal glycemic control as measured by HbA1c and capillary glucose measurements. [ Time Frame: Up to 40 weeks gestation ]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.
- Maternal hypoglycemia [ Time Frame: Up to 40 weeks gestation ]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.
- Maternal weight gain [ Time Frame: Up to 40 weeks gestation ]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.
- Maternal insulin doses [ Time Frame: Up to 40 weeks gestation ]Maternal insulin doses (overall amount and number of patients that are taking 'high' insulin doses defined as 2 Units/kg or more per day)
- Pre-eclampsia, and/or gestational hypertension [ Time Frame: Up to 40 weeks gestation ]
Gestational hypertension: New onset of hypertension in pregnancy ≥ 20 weeks gestation in a woman with previously normal blood pressure, defined as diastolic blood pressure of ≥ 90 mmHg, taken on 2 occasions or placed on antihypertensive medication and without proteinuria.
Pre-eclampsia: please refer to protocol for definition
- Sepsis [ Time Frame: Up to 28 days after birth ]A positive blood and/or cerebral spinal fluid culture during the neonatal hospital stay.
- Hyperbilirubinemia [ Time Frame: First 7 days of life ]Significant jaundice was present based on bilirubin levels requiring treatment with phototherapy> 6 continuous hours, or an exchange transfusion, or receiving intravenous gamma globulin, or requiring readmission into hospital during the first 7 days of life.
- Number of hospitalizations [ Time Frame: Up to 40 weeks gestation ]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.
- Rate of caesarean-section [ Time Frame: Up to 40 weeks gestation ]
- Duration of hospital stay for infant. [ Time Frame: Up to 28 days after birth ]Duration of hospital stay for infant associated with his/her birth u
Original Secondary Outcome:
- Large for gestational age (LGA) infants [ Time Frame: Up to 24 hours after birth ]Defined as greater than the 90th percentile for weight, based on the National canadian fetal growth standards for singleton boys and girls.
- Pregnancy loss [ Time Frame: Up to 40 weeks gestation ]Spontaneous abortion defined as death of a fetus at <20 weeks gestation; Stillbirth defined as death of a fetus with a birth weight ≥ 500g or at ≥ 20 wks gestational age regardless of birth weight; Neonatal death defined as death of a live born infant within the first 28 days of life or prior to hospital discharge, whichever is later.
- Preterm birth [ Time Frame: Up to 37 weeks gestation ]Birth < 37 weeks gestation
- Respiratory distress [ Time Frame: within 72 hours after birth ]Given surfactant via an endotracheal tube and/or requiring assisted positive pressure ventilation within 72 hours after birth.
- Neonatal hypoglycemia [ Time Frame: NICU admission >24 hours ]A plasma gluclose <2.6 mmol/L on one or more occasions, starting at 30-60 minutes after birth, and necessitating intravenous dextrose within the first 48 hours of life.
- NICU admission >24 hours [ Time Frame: NICU admission >24 hours ]Admission to a neonatal intensive or special care unit for > 24 hours during the initial hospitalization after birth
- Cord blood gases <7.0 [ Time Frame: Within 4 hours of birth ]
- Hyperinsulinemia as measured by elevated cord blood C-peptide [ Time Frame: Within 4 hours of birth ]A cord serum C-peptide value > 1.7 ug/L (which is >90th percentile of values for the total cohort of participants in the HAPO trial) will be defined as hyperinsulinemia.
- Maternal glycemic control as measured by HbA1c and capillary glucose measurements. [ Time Frame: Up to 40 weeks gestation ]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.
- Maternal hypoglycemia [ Time Frame: Up to 40 weeks gestation ]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.
- Maternal weight gain [ Time Frame: Up to 40 weeks gestation ]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.
- Maternal insulin doses [ Time Frame: Up to 40 weeks gestation ]Maternal insulin doses (overall amount and number of patients that are taking 'high' insulin doses defined as 2 Units/kg or more per day)
- Pre-eclampsia, and/or gestational hypertension [ Time Frame: Up to 40 weeks gestation ]
Gestational hypertension: New onset of hyperstension (diastolic of 90 mm Hg or higher) in pregnancy after 20 weeks gestation in a woman with previously normal blood pressure (124, 125).
Pre-eclampsia: new-onset proteinuria, Eclampsia (Seizures in pregnancy), Elevated liver function tests, Decreased platelet count < 100 x 109/L, Elevated serum creatinine (> 80 mmol/L) or small for gestational age infant (birth weight less than 10%).
- Sepsis [ Time Frame: Up to 28 days after birth ]A positive blood and/or cerebral spinal fluid culture during the neonatal hospital stay.
- Hyperbilirubinemia [ Time Frame: First 7 days of life ]Significant jaundice was present based on bilirubin levels requiring treatment with phototherapy> 6 continuous hours, or an exchange transfusion, or receiving intravenous gamma globulin, or requiring readmission into hospital during the first 7 days of life.
- Number of hospitalizations [ Time Frame: Up to 40 weeks gestation ]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.
- Rate of caesarean-section [ Time Frame: Up to 40 weeks gestation ]
- Duration of hospital stay for infant. [ Time Frame: Up to 28 days after birth ]
- Large for gestational age (LGA) infants [ Time Frame: Up to 24 hours after birth ]