A randomised, 52-week, treat-to-target trial comparing insulin detemir with insulin glargine when administered as add-on to glucose-lowering drugs in insulin-naive people with type 2 diabetes

Diabetologia. 2008 Mar;51(3):408-16. doi: 10.1007/s00125-007-0911-x. Epub 2008 Jan 16.

Abstract

Aims/hypothesis: This 52-week multinational, randomised, open-label, parallel-group, non-inferiority trial compared clinical outcomes following supplementation of oral glucose-lowering drugs with basal insulin analogues detemir and glargine in type 2 diabetic patients.

Methods: Insulin-naive adults (n=582, HbA(1c) 7.5-10.0%, BMI <or= 40.0 kg/m(2)) were randomised 1:1 to receive insulin detemir or glargine once daily (evening) actively titrated to target fasting plasma glucose (FPG) <or= 6.0 mmol/l. An additional morning insulin detemir dose was permitted if pre-dinner plasma glucose (PG) was >7.0 mmol/l after achieving FPG <7.0 mmol/l. Due to labelling restrictions, no second glargine dose was allowed.

Results: Baseline HbA(1c) decreased from 8.6 to 7.2 and 7.1% (NS) with detemir and glargine, respectively. FPG improved from 10.8 to 7.1 and 7.0 mmol/l (NS), respectively. With detemir, 45% of participants completed the study on once daily dosing and 55% on twice daily dosing, with no difference in HbA(1c). Overall, 52% of participants achieved HbA(1c) <or= 7.0%: 33% (detemir) and 35% (glargine) without hypoglycaemia. Within-participant variability for self-monitored FPG and pre-dinner PG did not differ by insulin treatment, nor did the relative risk of overall or nocturnal hypoglycaemia. Modest reductions in weight gain were seen with detemir vs glargine in completers (3.0 vs 3.9 kg, p=0.01) and in the intention-to-treat population (2.7 vs 3.5 kg, p=0.03), primarily related to completers on once-daily detemir. Mean daily detemir dose was higher (0.78 U/kg [0.52 with once daily dosing, 1.00 U/kg with twice daily dosing]) than glargine (0.44 IU/kg). Injection site reactions were more frequent with detemir (4.5 vs 1.4%).

Conclusions/interpretation: Supplementation of oral agents with detemir or glargine achieves clinically important improvements in glycaemic control with low risk of hypoglycaemia. Non-inferiority was demonstrated for detemir using higher insulin doses (mainly patients on twice daily dosing); weight gain was somewhat reduced with once daily insulin detemir.

Trial registration: ClinicalTrials.gov NCT00283751.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Glucose Self-Monitoring
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / analogs & derivatives*
  • Insulin / therapeutic use
  • Insulin Detemir
  • Insulin Glargine
  • Insulin, Long-Acting
  • Male
  • Middle Aged

Substances

  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Insulin, Long-Acting
  • Insulin Glargine
  • Insulin Detemir

Associated data

  • ClinicalTrials.gov/NCT00283751