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Safety, effectiveness, and cost effectiveness of long acting versus intermediate acting insulin for patients with type 1 diabetes: systematic review and network meta-analysis

BMJ 2014; 349 doi: (Published 01 October 2014) Cite this as: BMJ 2014;349:g5459
  1. Andrea C Tricco, research scientist1,
  2. Huda M Ashoor, research coordinator1,
  3. Jesmin Antony, research coordinator1,
  4. Joseph Beyene, biostatistician2,
  5. Areti Angeliki Veroniki, post-doctoral fellow1,
  6. Wanrudee Isaranuwatchai, research associate1,
  7. Alana Harrington, research assistant1,
  8. Charlotte Wilson, research coordinator1,
  9. Sophia Tsouros, research assistant1,
  10. Charlene Soobiah, graduate student1,
  11. Catherine H Yu, endocrinologist1,
  12. Brian Hutton, research scientist3,
  13. Jeffrey S Hoch, associate professor of health policy1,
  14. Brenda R Hemmelgarn, professor of medicine4,
  15. David Moher, research scientist3,
  16. Sumit R Majumdar, professor of medicine5,
  17. Sharon E Straus, professor of medicine16
  1. 1Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, ON, M5B 1T8, Canada
  2. 2Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, L8S 4K1, Canada
  3. 3Clinical Epidemiology Program, Ottawa Hospital Research Institute and Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8L6, Canada
  4. 4Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, T2N 4Z6, Canada
  5. 5Department of Medicine, University of Alberta, Edmonton, AB, T6G 2R3, Canada
  6. 6Department of Geriatric Medicine, University of Toronto, Toronto, ON, M5S 1A1, Canada
  1. Correspondence to: S E Straus sharon.straus{at}
  • Accepted 22 August 2014


Objective To examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes.

Design Systematic review and network meta-analysis.

Data sources Medline, Cochrane Central Register of Controlled Trials, Embase, and grey literature were searched through January 2013.

Study selection 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.

Systematic review registration PROSPERO CRD42013003610.


  • We thank the British Columbia Ministry of Health for requesting this systematic review and for their useful feedback on the review conception. We thank Laure Perrier for doing the literature searches, Becky Skidmore for peer reviewing the Medline search strategy, and Alissa Epworth for doing the forward citation scanning and the PubMed related article searches. Finally, we thank Maggie Chen for providing feedback on our original proposal; Kednapa Thavorn for appraising the quality of cost effectiveness studies; Judy Tran for locating full text articles; Geetha Sanmugalingham for screening some titles and abstracts; Wing Hui for scanning the reference lists of some included studies, helping to generate the data tables, and formatting the manuscript; and Wasifa Zarin for helping to reformat the paper.

  • Contributors: ACT conceived and designed the study, helped to obtain funding for the study, screened literature for inclusion, abstracted data from included studies, and wrote the manuscript. HMA coordinated the study, screened the literature search results, and abstracted data. JB, AAV, and WI analyzed the results and helped to draft sections of the paper. AH, CS, CW, JA, and ST helped to screen the literature and/or abstracted data. CHY, BH, BRH, DM, and SRM helped to obtain funding for the study and to conceive the study. SES conceived and designed the study, obtained the funding, and helped to write the draft paper. All authors interpreted the results and read, edited, and approved the final paper. SES is the guarantor.

  • Funding: This systematic review was funded by the Canadian Institutes for Health Research/Drug Safety and Effectiveness Network (CIHR/DSEN). The study funder had no role in the design, conduct, analysis, and decision to submit for publication. ACT and BH are funded by CIHR/DSEN new investigator awards in knowledge synthesis. JB holds the John D Cameron endowed chair in the genetic determinants of chronic diseases, Department of Clinical Epidemiology and Biostatistics, McMaster University. DM is funded by a University of Ottawa Research chair. SRM is the endowed chair in patient health management (supported by the Faculties of Medicine and Dentistry and Pharmacy and Pharmaceutical Sciences) and holds a health scholar salary award (supported by Alberta Heritage Foundation for Medical Research and Alberta Innovates - Health Solutions). SES is funded by a tier 1 Canada research chair in knowledge translation.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: this was work funded by the Canadian Institutes for Health Research; no financial relationships with any organization that might have an interest in the submitted work in the previous three years; no relationships or activities that could appear to have influenced the submitted work.

  • Ethics approval: Not needed.

  • Declaration of transparency: The lead author (study guarantor) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

  • Data sharing: The data set and literature search are available from the corresponding author at Sharon.straus{at}

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