Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus

Cochrane Database Syst Rev. 2007 Apr 18;(2):CD005613. doi: 10.1002/14651858.CD005613.pub3.


Background: Despite indications from epidemiological trials that higher blood glucose concentrations are associated with a higher risk for developing micro- and macrovascular complications, evidence for a beneficial effect of antihyperglycaemic therapy in patients with type 2 diabetes mellitus is conflicting. Two large studies, the United Kingdom Prospective Diabetes Study (UKPDS) and the University Group Diabetes Program (UGDP), did not find a reduction of cardiovascular endpoints through improvement of metabolic control. The theoretical benefits of newer insulin analogues might result in fewer macrovascular and microvascular events.

Objectives: To assess the effects of long-term treatment with long-acting insulin analogues (insulin glargine and insulin detemir) compared to NPH insulin in patients with type 2 diabetes mellitus.

Search strategy: Studies were obtained from computerised searches of MEDLINE, EMBASE, The Cochrane Library and communication with experts in the field as well as insulin producing companies.

Selection criteria: Studies were included if they were randomised controlled trials in adults with diabetes mellitus type 2 and had a trial duration of at least 24 weeks.

Data collection and analysis: Two authors independently assessed trial quality and extracted data. Pooling of studies by means of random-effects meta-analyses was performed.

Main results: Six studies comparing insulin glargine to NPH (Neutral Protamine Hagedorn) insulin and two studies comparing insulin detemir to NPH insulin were identified. In these trials, 1715 patients were randomised to insulin glargine and 578 patients to insulin detemir. Duration of the included trials ranged from 24 to 52 weeks. Metabolic control, measured by glycosylated haemoglobin A1c (HbA1c) as a surrogate endpoint, and adverse effects did not differ in a clinical relevant way between treatment groups. While no statistically significant difference for severe hypoglycaemia rates was shown in any of the trials, the rate of symptomatic, overall and nocturnal hypoglycaemia was statistically significantly lower in patients treated with either insulin glargine or detemir. No evidence for a beneficial effect of long-acting analogues on patient-oriented outcomes like mortality, morbidity, quality of life or costs could be obtained.

Authors' conclusions: Our analysis suggests, if at all only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2 treated with "basal" insulin regarding symptomatic nocturnal hypoglycaemic events. Until long-term efficacy and safety data are available, we suggest a cautious approach to therapy with insulin glargine or detemir.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / analogs & derivatives
  • Insulin / therapeutic use
  • Insulin Detemir
  • Insulin Glargine
  • Insulin, Isophane / therapeutic use*
  • Insulin, Long-Acting / therapeutic use*
  • Randomized Controlled Trials as Topic


  • Hypoglycemic Agents
  • Insulin
  • Insulin, Long-Acting
  • Insulin Glargine
  • Insulin Detemir
  • Insulin, Isophane