title: Safety, effectiveness, and cost effectiveness of long acting versus intermediate acting insulin for patients with type 1 diabetes: systematic review and network meta-analysis.
abstract: OBJECTIVE
  To examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes.
  
  
  METHODS
  Systematic review and network meta-analysis.
  
  
  METHODS
  Medline, Cochrane Central Register of Controlled Trials, Embase, and grey literature were searched through January 2013.
  
  
  METHODS
  Randomized controlled trials or non-randomized studies of long acting (glargine, detemir) and intermediate acting (neutral protamine Hagedorn (NPH), lente) insulin for adults with type 1 diabetes were included.
  
  
  RESULTS
  39 studies (27 randomized controlled trials including 7496 patients) were included after screening of 6501 titles/abstracts and 190 full text articles. Glargine once daily, detemir once daily, and detemir once/twice daily significantly reduced hemoglobin A1c compared with NPH once daily in network meta-analysis (26 randomized controlled trials, mean difference -0.39%, 95% confidence interval -0.59% to -0.19%; -0.26%, -0.48% to -0.03%; and -0.36%, -0.65% to -0.08%; respectively). Differences in network meta-analysis were observed between long acting and intermediate acting insulin for severe hypoglycemia (16 randomized controlled trials; detemir once/twice daily versus NPH once/twice daily: odds ratio 0.62, 95% confidence interval 0.42 to 0.91) and weight gain (13 randomized controlled trials; detemir once daily versus NPH once/twice daily: mean difference 4.04 kg, 3.06 to 5.02 kg; detemir once/twice daily versus NPH once daily: -5.51 kg, -6.56 to -4.46 kg; glargine once daily versus NPH once daily: -5.14 kg, -6.07 to -4.21). Compared with NPH, detemir was less costly and more effective in 3/14 cost effectiveness analyses and glargine was less costly and more effective in 2/8 cost effectiveness analyses. The remaining cost effectiveness analyses found that detemir and glargine were more costly but more effective than NPH. Glargine was not cost effective compared with detemir in 2/2 cost effectiveness analyses.
  
  
  CONCLUSIONS
  Long acting insulin analogs are probably superior to intermediate acting insulin analogs, although the difference is small for hemoglobin A1c. Patients and their physicians should tailor their choice of insulin according to preference, cost, and accessibility.
  
  
  BACKGROUND
  PROSPERO CRD42013003610.
authors.affiliation: Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, M5B 1T8, Canada.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Tricco
authors.affiliation: Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, M5B 1T8, Canada.
authors.forename: Huda M
authors.initials: HM
authors.lastname: Ashoor
authors.affiliation: Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, M5B 1T8, Canada.
authors.forename: Jesmin
authors.initials: J
authors.lastname: Antony
authors.affiliation: Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, L8S 4K1, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Beyene
authors.affiliation: Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, M5B 1T8, Canada.
authors.forename: Areti Angeliki
authors.initials: AA
authors.lastname: Veroniki
authors.affiliation: Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, M5B 1T8, Canada.
authors.forename: Wanrudee
authors.initials: W
authors.lastname: Isaranuwatchai
authors.affiliation: Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, M5B 1T8, Canada.
authors.forename: Alana
authors.initials: A
authors.lastname: Harrington
authors.affiliation: Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, M5B 1T8, Canada.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Wilson
authors.affiliation: Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, M5B 1T8, Canada.
authors.forename: Sophia
authors.initials: S
authors.lastname: Tsouros
authors.affiliation: Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, M5B 1T8, Canada.
authors.forename: Charlene
authors.initials: C
authors.lastname: Soobiah
authors.affiliation: Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, M5B 1T8, Canada.
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Yu
authors.affiliation: Clinical Epidemiology Program, Ottawa Hospital Research Institute and Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8L6, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Hutton
authors.affiliation: Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, M5B 1T8, Canada.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Hoch
authors.affiliation: Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, T2N 4Z6, Canada.
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Hemmelgarn
authors.affiliation: Clinical Epidemiology Program, Ottawa Hospital Research Institute and Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8L6, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Moher
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, AB, T6G 2R3, Canada.
authors.forename: Sumit R
authors.initials: SR
authors.lastname: Majumdar
authors.affiliation: Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, M5B 1T8, Canada Department of Geriatric Medicine, University of Toronto, Toronto, ON, M5S 1A1, Canada sharon.straus@utoronto.ca.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Straus
mesh_terms: D003362:Cost-Benefit Analysis; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000191:economics* / Q000627:therapeutic use*; D049528:Insulin, Long-Acting / Q000191:economics* / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting