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Intervention Review

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Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus

  1. Bianca Hemmingsen1,*,
  2. Søren S Lund2,
  3. Christian Gluud3,
  4. Allan Vaag4,
  5. Thomas P Almdal5,
  6. Jørn Wetterslev6

Editorial Group: Cochrane Metabolic and Endocrine Disorders Group

Published Online: 11 NOV 2013

Assessed as up-to-date: 8 DEC 2012

DOI: 10.1002/14651858.CD008143.pub3


How to Cite

Hemmingsen B, Lund SS, Gluud C, Vaag A, Almdal TP, Wetterslev J. Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No.: CD008143. DOI: 10.1002/14651858.CD008143.pub3.

Author Information

  1. 1

    Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen, Denmark

  2. 2

    Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany

  3. 3

    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, The Cochrane Hepato-Biliary Group, Copenhagen, Denmark

  4. 4

    Rigshospitalet and Copenhagen University, Department of Endocrinology, Diabetes and Metabolism, København N, Denmark

  5. 5

    Copenhagen University Hospital Gentofte, Department of Medicine F, Hellerup, Denmark

  6. 6

    Rigshospitalet, Copenhagen University Hospital, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Copenhagen, Denmark

*Bianca Hemmingsen, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, DK-2100, Denmark. biancahemmingsen@hotmail.com. bh@ctu.rh.dk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 11 NOV 2013

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This is not the most recent version of the article. View current version (29 JUL 2015)

[Figure 1]
Figure 1. Study flow diagram.
[Figure 2]
Figure 2. Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
[Figure 3]
Figure 3. Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
[Figure 4]
Figure 4. Trial sequential for all-cause mortality for all trials. Diversity-adjusted required information size of 46,305 participants calculated on basis of proportion of mortality of 9.6% in the conventional glucose control group, relative risk reduction of 10% in the intensive glycaemic control group, alpha = 5%, beta = 20%, and diversity = 39%. Actually accrued number was 33,806 participants, 73% of required information size. Horisontal green lines illustrate conventional levels of statistical significance (P = 0.05). Blue cumulative Z-curve does not cross trial sequential monitoring boundaries for benefit or harm, but boundaries for futility (inner wedge) are crossed.
[Figure 5]
Figure 5. Funnel plot of comparison: 1 Intensive glycaemic control versus conventional glycaemic control, outcome: 1.1 All-cause mortality.
[Figure 6]
Figure 6. Trial sequential for cardiovascular mortality for all trials. Diversity-adjusted required information size of 115,094 participants calculated on basis of proportion of cardiovascular mortality of 4.5% in the conventional glucose control group, relative risk reduction of 10% in the intensive glycaemic control group, alpha = 5%, beta = 20%, and diversity = 45%. Actually accrued number was 33,658 participants, 29% of required information size. Horisontal green lines illustrate conventional levels of statistical significance (P = 0.05). Blue cumulative Z-curve does not cross trial sequential monitoring boundaries for benefit or harm, or reach futility.
[Analysis 1.1]
Analysis 1.1. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 1 All-cause mortality.
[Analysis 1.2]
Analysis 1.2. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 2 All-cause mortality; stratified according to risk of bias.
[Analysis 1.3]
Analysis 1.3. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 3 All-cause mortality; stratified according to sequence generation.
[Analysis 1.4]
Analysis 1.4. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 4 All-cause mortality; stratified according to allocation concealment.
[Analysis 1.5]
Analysis 1.5. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 5 All-cause mortality; stratified according to blinding (study level).
[Analysis 1.6]
Analysis 1.6. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 6 All-cause mortality; stratified according to outcome data (outcome level).
[Analysis 1.7]
Analysis 1.7. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 7 All-cause mortality; stratified according to outcome reporting bias (study level).
[Analysis 1.8]
Analysis 1.8. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 8 All-cause mortality; stratified according to academic bias.
[Analysis 1.9]
Analysis 1.9. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 9 All-cause mortality; stratified according to source of funding.
[Analysis 1.10]
Analysis 1.10. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 10 All-cause mortality; stratified according to study duration.
[Analysis 1.11]
Analysis 1.11. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 11 All-cause mortality; stratified according to diagnostic criteria.
[Analysis 1.12]
Analysis 1.12. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 12 All-cause mortality; stratified according to intervention.
[Analysis 1.13]
Analysis 1.13. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 13 All-cause mortality; hazard ratio.
[Analysis 1.14]
Analysis 1.14. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 14 All-cause mortality; available case.
[Analysis 1.15]
Analysis 1.15. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 15 All-cause mortality; best-case scenario.
[Analysis 1.16]
Analysis 1.16. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 16 All-cause mortality; worst-case scenario.
[Analysis 1.17]
Analysis 1.17. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 17 Cardiovascular mortality.
[Analysis 1.18]
Analysis 1.18. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 18 Cardiovascular mortality; stratified according to risk of bias.
[Analysis 1.19]
Analysis 1.19. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 19 Cardiovascular mortality; stratified according to sequence generation.
[Analysis 1.20]
Analysis 1.20. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 20 Cardiovascular mortality; stratified according to allocation concealment.
[Analysis 1.21]
Analysis 1.21. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 21 Cardiovascular mortality; stratified according to blinding (study level).
[Analysis 1.22]
Analysis 1.22. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 22 Cardiovascular mortality; stratified according to outcome data (outcome level).
[Analysis 1.23]
Analysis 1.23. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 23 Cardiovascular mortality; stratified according to outcome reporting bias (study level).
[Analysis 1.24]
Analysis 1.24. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 24 Cardiovascular mortality; stratified according to academic bias.
[Analysis 1.25]
Analysis 1.25. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 25 Cardiovascular mortality; stratified according to source of funding.
[Analysis 1.26]
Analysis 1.26. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 26 Cardiovascular mortality; stratified according to study duration.
[Analysis 1.27]
Analysis 1.27. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 27 Cardiovascular mortality; stratified according to diagnostic criteria.
[Analysis 1.28]
Analysis 1.28. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 28 Cardiovascular mortality; stratified according to intervention.
[Analysis 1.29]
Analysis 1.29. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 29 Cardiovascular mortality; hazard ratio.
[Analysis 1.30]
Analysis 1.30. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 30 Cardiovascular mortality; available case.
[Analysis 1.31]
Analysis 1.31. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 31 Cardiovascular mortality; best-case scenario.
[Analysis 1.32]
Analysis 1.32. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 32 Cardiovascular mortality; worst-case scenario.
[Analysis 1.33]
Analysis 1.33. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 33 Macrovascular complications.
[Analysis 1.34]
Analysis 1.34. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 34 Macrovascular complications; stratified according to intervention.
[Analysis 1.35]
Analysis 1.35. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 35 Non-fatal myocardial infarction.
[Analysis 1.36]
Analysis 1.36. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 36 Non-fatal myocardial infarction; stratified according to study duration.
[Analysis 1.37]
Analysis 1.37. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 37 Non-fatal myocardial infarction; stratified according to risk of bias.
[Analysis 1.38]
Analysis 1.38. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 38 Non-fatal myocardial infarction; stratified according to source of funding.
[Analysis 1.39]
Analysis 1.39. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 39 Non-fatal myocardial infarction; stratified according to diagnostic criteria.
[Analysis 1.40]
Analysis 1.40. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 40 Non-fatal myocardial infarction; stratified according to intervention.
[Analysis 1.41]
Analysis 1.41. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 41 Non-fatal myocardial infarction; available case.
[Analysis 1.42]
Analysis 1.42. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 42 Non-fatal myocardial infarction; best-case scenario.
[Analysis 1.43]
Analysis 1.43. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 43 Non-fatal myocardial infarction; worst-case scenario.
[Analysis 1.44]
Analysis 1.44. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 44 Non-fatal stroke.
[Analysis 1.45]
Analysis 1.45. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 45 Non-fatal stroke; stratified according to intervention.
[Analysis 1.46]
Analysis 1.46. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 46 Amputation of lower extremity.
[Analysis 1.47]
Analysis 1.47. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 47 Amputation of lower extremity; stratified according to intervention.
[Analysis 1.48]
Analysis 1.48. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 48 Cardiac revascularization.
[Analysis 1.49]
Analysis 1.49. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 49 Cardiac revascularization; stratified according to intervention.
[Analysis 1.50]
Analysis 1.50. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 50 Peripheral revascularization.
[Analysis 1.51]
Analysis 1.51. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 51 Peripheral revascularization; stratified according to intervention.
[Analysis 1.52]
Analysis 1.52. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 52 Microvascular complications.
[Analysis 1.53]
Analysis 1.53. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 53 Microvascular complications; stratified according to intervention.
[Analysis 1.54]
Analysis 1.54. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 54 Nephropathy.
[Analysis 1.55]
Analysis 1.55. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 55 Nephropathy; stratified according to intervention.
[Analysis 1.56]
Analysis 1.56. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 56 End-stage renal disease.
[Analysis 1.57]
Analysis 1.57. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 57 End-stage renal disease; stratified according to intervention.
[Analysis 1.58]
Analysis 1.58. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 58 Retinopathy.
[Analysis 1.59]
Analysis 1.59. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 59 Retinopathy; stratified according to intervention.
[Analysis 1.60]
Analysis 1.60. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 60 Retinal photocoagulation.
[Analysis 1.61]
Analysis 1.61. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 61 Retinal photocoagulation; stratified according to intervention.
[Analysis 1.62]
Analysis 1.62. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 62 Adverse events.
[Analysis 1.63]
Analysis 1.63. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 63 Serious adverse events; stratified according to intervention.
[Analysis 1.64]
Analysis 1.64. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 64 Drop-outs due to adverse events; stratified according to intervention.
[Analysis 1.65]
Analysis 1.65. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 65 Congestive heart failure.
[Analysis 1.66]
Analysis 1.66. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 66 Congestive heart failure; stratified after intervention.
[Analysis 1.67]
Analysis 1.67. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 67 Hypoglycaemia.
[Analysis 1.68]
Analysis 1.68. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 68 Mild hypoglycaemia; stratified according to intervention.
[Analysis 1.69]
Analysis 1.69. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 69 Severe hypoglycaemia; stratified according to intervention.
[Analysis 1.70]
Analysis 1.70. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 70 Health-related quality of life; EQ5D.
[Analysis 1.71]
Analysis 1.71. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 71 Quality of life: mental component.
[Analysis 1.72]
Analysis 1.72. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 72 Quality of life: physical component.
[Analysis 1.73]
Analysis 1.73. Comparison 1 Intensive glycaemic control versus conventional glycaemic control, Outcome 73 Cost of intervention.