title: Metformin in women with type 2 diabetes in pregnancy (MiTy): a multi-center randomized controlled trial.
abstract: The incidence of type 2 diabetes in pregnancy is rising and rates of serious adverse maternal and fetal outcomes remain high. Metformin is a biguanide that is used as first-line treatment for non-pregnant patients with type 2 diabetes. We hypothesize that metformin use in pregnancy, as an adjunct to insulin, will decrease adverse outcomes by reducing maternal hyperglycemia, maternal insulin doses, maternal weight gain and gestational hypertension/pre-eclampsia. In addition, since metformin crosses the placenta, metformin treatment of the fetus may have a direct beneficial effect on neonatal outcomes. Our aim is to compare the effectiveness of the addition of metformin to insulin, to standard care (insulin plus placebo) in women with type 2 diabetes in pregnancy.
  
  
  
  The MiTy trial is a multi-centre randomized trial currently enrolling pregnant women with type 2 diabetes, who are on insulin, between the ages of 18-45, with a gestational age of 6 weeks 0 days to 22 weeks 6 days. In this randomized, double-masked, parallel placebo-controlled trial, after giving informed consent, women are randomized to receive either metformin 1,000 mg twice daily or placebo twice daily. A web-based block randomization system is used to assign women to metformin or placebo in a 1:1 ratio, stratified for site and body mass index. The primary outcome is a composite neonatal outcome of pregnancy loss, preterm birth, birth injury, moderate/severe respiratory distress, neonatal hypoglycemia, or neonatal intensive care unit admission longer than 24 h. Secondary outcomes are large for gestational age, cord blood gas pH < 7.0, congenital anomalies, hyperbilirubinemia, sepsis, hyperinsulinemia, shoulder dystocia, fetal fat mass, as well as maternal outcomes: maternal weight gain, maternal insulin doses, maternal glycemic control, maternal hypoglycemia, gestational hypertension, preeclampsia, cesarean section, number of hospitalizations during pregnancy, and duration of hospital stays. The trial aims to enroll 500 participants.
  
  
  
  The results of this trial will inform endocrinologists, obstetricians, family doctors, and other healthcare professionals caring for women with type 2 diabetes in pregnancy, as to the benefits of adding metformin to insulin in this high risk population.
  
  
  
  ClinicalTrials.gov Identifier: no. NCT01353391 . Registered February 6, 2009.
authors.affiliation: Mount Sinai Hospital, 60 Murray St., Lebovic Building, Suite 5027, M5T 3L9, Toronto, Ontario, Canada. d.feig@utoronto.ca.|Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada. d.feig@utoronto.ca.|Department of Medicine, University of Toronto, Toronto, Canada. d.feig@utoronto.ca.
authors.forename: Denice S
authors.initials: DS
authors.lastname: Feig
authors.affiliation: Mount Sinai Hospital, 60 Murray St., Lebovic Building, Suite 5027, M5T 3L9, Toronto, Ontario, Canada.|Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada.
authors.forename: Kellie
authors.initials: K
authors.lastname: Murphy
authors.affiliation: Sunnybrook Health Sciences Centre Toronto, Toronto, Canada.|Sunnybrook Research Institute Toronto, Toronto, Ontario, Canada.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Asztalos
authors.affiliation: University Health Network, Toronto, Canada.|Institute for Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Tomlinson
authors.affiliation: Sunnybrook Research Institute Toronto, Toronto, Ontario, Canada.|The Centre for Mother, Infant and Child Research (CMICR), Toronto, Ontario, Canada.
authors.forename: Johanna
authors.initials: J
authors.lastname: Sanchez
authors.affiliation: Mount Sinai Hospital, 60 Murray St., Lebovic Building, Suite 5027, M5T 3L9, Toronto, Ontario, Canada.|Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.affiliation: Mount Sinai Hospital, 60 Murray St., Lebovic Building, Suite 5027, M5T 3L9, Toronto, Ontario, Canada.|Department of Paediatics, University of Toronto, Toronto, Canada.
authors.forename: Arne
authors.initials: A
authors.lastname: Ohlsson
authors.affiliation: University of Alberta, Edmonton, Canada.
authors.forename: Edmond A
authors.initials: EA
authors.lastname: Ryan
authors.affiliation: Mount Sinai Hospital, 60 Murray St., Lebovic Building, Suite 5027, M5T 3L9, Toronto, Ontario, Canada.|Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: I George
authors.initials: IG
authors.lastname: Fantus
authors.affiliation: Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Armson
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Canada.|Women's College Hospital, Toronto, Ontario, Canada.
authors.forename: Lorraine L
authors.initials: LL
authors.lastname: Lipscombe
authors.affiliation: Sunnybrook Health Sciences Centre Toronto, Toronto, Canada.|Sunnybrook Research Institute Toronto, Toronto, Ontario, Canada.|The Centre for Mother, Infant and Child Research (CMICR), Toronto, Ontario, Canada.
authors.forename: Jon F R
authors.initials: JF
authors.lastname: Barrett
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D002985:Clinical Protocols; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000139:chemically induced; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced; D011256:Pregnancy Outcome; D011254:Pregnancy in Diabetics / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin
keywords: Diabetes Mellitus; Diabetes Mellitus Type 2; Metformin; Pregnancy; Pregnancy in diabetics; Pregnancy outcome; Randomized controlled trial