Long-acting insulin analogues vs. NPH human insulin in type 1 diabetes. A meta-analysis

Diabetes Obes Metab. 2009 Apr;11(4):372-8. doi: 10.1111/j.1463-1326.2008.00976.x.


Aim: Basal insulin in type 1 diabetes can be provided using either NPH (Neutral Protamine Hagedorn) human insulin or long-acting insulin analogues, which are supposed to warrant a better metabolic control with reduced hypoglycaemic risk. Aim of this meta-analysis is the assessment of differences with respect to HbA1c (Glycated hemoglobin), incidence of hypoglycaemia, and weight gain, between NPH human insulin and each long-acting analogue.

Methods: Of 285 randomized controlled trials with a duration > 12 weeks comparing long-acting insulin analogues (detemir or glargine) with NPH insulin in type 1 diabetic patients identified through Medline search and searches on www.clinicaltrials.gov, 20 met eligibility criteria (enrolling 3693 and 2485 in the long-acting analogues and NPH group respectively). Data on HbA1c and body mass index at endpoint, and incidence of any, nocturnal and severe hypoglycaemia, were extracted and meta-analysed.

Results: Long-acting analogues had a small, but significant effect on HbA1c [-0.07 (-0.13; -0.01)%; p = 0.026], in comparison with NPH human insulin. When analysing the effect of long-acting analogues on body weight, detemir was associated with a significantly smaller weight gain than human insulin [by 0.26 (0.06;0.47) kg/m2; p = 0.012]. Long-acting analogues were associated with a reduced risk for nocturnal and severe hypoglycaemia [OR (Odd Ratio, 95% Confidence Intervals) 0.69 (0.55; 0.86), and OR 0.73 (0.60; 0.89) respectively; all p < 0.01].

Conclusions: The switch from NPH to long-acting analogues as basal insulin replacement in type 1 diabetic patients had a small effect on HbA1c, and also reduced the risk of nocturnal and severe hypoglycaemia.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Body Mass Index
  • Child
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Insulin, Isophane / adverse effects
  • Insulin, Isophane / therapeutic use*
  • Insulin, Long-Acting / adverse effects
  • Insulin, Long-Acting / therapeutic use*
  • Randomized Controlled Trials as Topic


  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin, Long-Acting
  • Insulin, Isophane