Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus

Cochrane Database Syst Rev. 2006 Apr 19;(2):CD003287. doi: 10.1002/14651858.CD003287.pub4.


Background: Short acting insulin analogue use for diabetic patients is still controversial, as reflected in many scientific debates.

Objectives: To assess the effects of short acting insulin analogues versus regular human insulin.

Search strategy: The Cochrane Library (Issue 3, 2005), MEDLINE, EMBASE until September 2005.

Selection criteria: Randomised controlled trials with an intervention duration of at least 4 weeks.

Data collection and analysis: Trial selection and evaluation of study quality was done independently by two reviewers.

Main results: Altogether 8274 participants took part in 49 randomised controlled studies. Most studies were of poor methodological quality. In patients with type 1 diabetes, the weighted mean difference (WMD) of HbA1c was -0.1% (95% CI: -0.2 to -0.1) in favour of insulin analogue, whereas in patients with type 2 diabetes the WMD was 0.0% (95% CI: -0.1 to 0.0). In subgroup analyses of different types of interventions in type 1 diabetic patients, the WMD in HbA1c was -0.2% (95% CI: -0.3 to -0.1) in favour of insulin analogue in studies using continuous subcutaneous insulin injections (CSII), whereas for conventional intensified insulin therapy (IIT) studies the WMD in HbA1c was -0.1% (95% CI: -0.1 to 0.0). The WMD of the overall mean hypoglycaemic episodes per patient per month was -0.2 (95% CI: -1.1 to 0.7) and -0.2 (95% CI: -0.5 to 0.1) for analogues in comparison to regular insulin in patients with type 1 diabetes and type 2 diabetes, respectively. For studies in type 1 diabetes patients the incidence of severe hypoglycaemia ranged from 0 to 247.3 (median 21.8) episodes per 100 person-years for insulin analogues and from 0 to 544 (median 46.1) for regular insulin, in type 2 the incidence ranged from 0 to 30.3 (median 0.3) episodes per 100 person-years for insulin analogues and from 0 to 50.4 (median 1.4) for regular insulin. No study was designed to investigate possible long term effects (e.g. mortality, diabetic complications), in particular in patients with diabetes related complications.

Authors' conclusions: Our analysis suggests only a minor benefit of short acting insulin analogues in the majority of diabetic patients treated with insulin. Until long term efficacy and safety data are available we suggest a cautious response to the vigorous promotion of insulin analogues. For safety purposes, we need a long-term follow-up of large numbers of patients and well designed studies in pregnant women to determine the safety profile for both the mother and the unborn child.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / analogs & derivatives
  • Insulin / therapeutic use*
  • Insulin Aspart
  • Insulin Lispro
  • Randomized Controlled Trials as Topic


  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Insulin Lispro
  • insulin glulisine
  • Insulin Aspart