title: Short- and long-term outcomes of metformin compared with insulin alone in pregnancy: a systematic review and meta-analysis.
abstract: To assess the short- and long-term maternal and fetal impact of metformin in pregnancy compared with insulin.
  
  
  
  We performed a comprehensive literature search of MEDLINE, EMBASE, BIOSIS, Cochrane Database of Systematic Reviews and ClinicalTrials.gov. Eligible studies were randomized control trials (RCTs) or follow-up of an RCT that: (1) compared metformin with insulin in pregnancy in women with gestational diabetes mellitus or Type 2 diabetes; and (2) reported maternal or fetal outcomes of interest. Two reviewers extracted the data, evaluated study quality and calculated pooled estimates.
  
  
  
  Sixteen studies (n = 2165 in quantitative analysis) were included. Metformin lowered the risk of neonatal hypoglycaemia [risk ratio (RR) = 0.63; 95% confidence interval (95% CI), 0.45 to 0.87], large for gestational age babies (RR = 0.80; 95% CI, 0.64 to 0.99), pregnancy-induced hypertension (RR = 0.56; 95% CI, 0.37 to 0.85) and total maternal pregnancy weight gain [mean difference (MD) -2.07; 95% CI -2.88 to -1.27]. Metformin did not increase preterm delivery (RR = 1.18; 95% CI 0.67 to 2.07), small for gestational age babies (RR = 1.20; 95% CI, 0.67 to 2.14), perinatal mortality (RR = 0.82; 95% CI, 0.17 to 3.92) or Caesarean section (RR = 0.97; 95% CI, 0.80 to 1.19). Long-term outcome information is limited.
  
  
  
  Our review found that metformin had no short-term adverse effects on pregnancy, potential benefits in the neonatal period, but limited long-term follow-up information. Prior to routine use, we recommend further follow-up studies of offspring exposed to metformin in utero.
authors.affiliation: Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Butalia
authors.affiliation: Department of Internal Medicine, St Joseph's Hospital, Comox, British Columbia, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Gutierrez
authors.affiliation: Departments of Pediatrics & Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Lodha
authors.affiliation: Knowledge Resource Service, Alberta Health Services, Calgary, Alberta, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Aitken
authors.affiliation: Department of Obstetrics and Gynecology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Zakariasen
authors.affiliation: Department of Medicine, University of Calgary, Calgary, Alberta, Canada.|Department of Obstetrics and Gynecology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Donovan
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D016640:Diabetes, Gestational / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007328:Insulin / Q000009:adverse effects* / Q000627:therapeutic use; D008687:Metformin / Q000009:adverse effects* / Q000627:therapeutic use; D011247:Pregnancy; D011256:Pregnancy Outcome; D011254:Pregnancy in Diabetics / Q000188:drug therapy* / Q000503:physiopathology; D011297:Prenatal Exposure Delayed Effects; D016032:Randomized Controlled Trials as Topic
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin