, Volume 57, Issue 7, pp 1325–1331

Basal insulin glargine and microvascular outcomes in dysglycaemic individuals: results of the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial

  • The ORIGIN trial investigators
  • Richard E. Gilbert
  • Johannes F. E. Mann
  • Markolf Hanefeld
  • Giatgen Spinas
  • Jackie Bosch
  • Salim Yusuf
  • Hertzel C. Gerstein



As glycaemia and the incidence of microvascular diabetes complications follow a log-linear relationship, it becomes increasingly difficult to demonstrate a microvascular benefit of glucose-lowering when the HbA1c level is close to normal.


The Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial randomised 12,537 people with diabetes, impaired glucose tolerance or impaired fasting glucose to receive standard glycaemic care or standard care with the addition of basal insulin glargine (A21Gly,B31Arg,B32Arg human insulin), targeting a fasting plasma glucose level ≤5.3 mmol/l. Microvascular outcomes during a median follow-up of 6.2 years were examined in participants whose baseline HbA1c was above or below the median of 6.4% (46.4 mmol/mol).


Allocation to the insulin glargine group reduced the incidence of the primary microvascular composite outcome of kidney and eye disease in participants whose baseline HbA1c level was ≥6.4% (46.4 mmol/mol; HR 0.90 [95% CI 0.81, 0.99]) but not in participants with a lower baseline HbA1c (HR 1.07 [95% CI 0.95, 1.20]; p value for interaction 0.031). In people whose baseline HbA1c level was ≥6.4% (46.4 mmol/mol), the median post-randomisation change in HbA1c was −0.65% (interquartile range −0.16, −0.91%) after allocation to insulin glargine and −0.33% (−0.83, 0.13%) after allocation to standard care (median HbA1c difference 0.33%; p < 0.0001). A smaller median difference of 0.22% was noted in people whose baseline HbA1c was <6.4% (p < 0.0001).


In patients with dysglycaemia, intervention targeting normal fasting glucose levels reduced HbA1c and attenuated the risk of microvascular outcomes in participants with a baseline HbA1c level ≥6.4% (46.4 mmol/mol). A neutral effect was seen in those with a lower baseline HbA1c level.

Trial registration:

ClinicalTrials.gov NCT00069784


Albuminuria Diabetic nephropathy Insulin glargine Microvascular Retinopathy 



Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation


Angiotensin-converting enzyme


Angiotensin receptor blocker


Interquartile range


Outcome Reduction with an Initial Glargine Intervention


UK Prospective Diabetes Study

Supplementary material

125_2014_3238_MOESM1_ESM.pdf (192 kb)
ESM Fig. 1(PDF 192 kb)
125_2014_3238_MOESM2_ESM.pdf (48 kb)
ESM Fig. 2(PDF 47 kb)
125_2014_3238_MOESM3_ESM.pdf (58 kb)
ESM Table 1(PDF 58 kb)
125_2014_3238_MOESM4_ESM.pdf (60 kb)
ESM Table 2(PDF 59 kb)
125_2014_3238_MOESM5_ESM.pdf (59 kb)
ESM Table 3(PDF 58 kb)
125_2014_3238_MOESM6_ESM.pdf (48 kb)
ESM Table 4(PDF 47 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • The ORIGIN trial investigators
  • Richard E. Gilbert
    • 1
    • 2
  • Johannes F. E. Mann
    • 3
  • Markolf Hanefeld
    • 4
  • Giatgen Spinas
    • 5
  • Jackie Bosch
    • 6
  • Salim Yusuf
    • 6
    • 7
  • Hertzel C. Gerstein
    • 6
    • 7
  1. 1.Division of Endocrinology, St Michael’s HospitalUniversity of TorontoTorontoCanada
  2. 2.Keenan Research Centre for Biomedical Sciences and Li Ka Shing Knowledge Institute, St Michael’s HospitalUniversity of TorontoTorontoCanada
  3. 3.Department of NephrologyFriedrich Alexander University, Erlangen and Munich General HospitalsMunichGermany
  4. 4.Centre for Clinical Studies, Gesellschaft für Wissens-und TechnologietransferTechnical University DresdenDresdenGermany
  5. 5.Division of Endocrinology, Diabetes and Clinical NutritionUniversity Hospital ZurichZurichSwitzerland
  6. 6.Population Health Research InstituteMcMaster University and Hamilton Health SciencesHamiltonCanada
  7. 7.Department of MedicineMcMaster UniversityHamiltonCanada

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