Comparison of pharmacokinetics and dynamics of the long-acting insulin analogs glargine and detemir at steady state in type 1 diabetes: a double-blind, randomized, crossover study

Diabetes Care. 2007 Oct;30(10):2447-52. doi: 10.2337/dc07-0002. Epub 2007 Jul 10.

Abstract

Objective: To compare pharmacokinetics and pharmacodynamics of insulin analogs glargine and detemir, 24 subjects with type 1 diabetes (aged 38 +/- 10 years, BMI 22.4 +/- 1.6 kg/m2, and A1C 7.2 +/- 0.7%) were studied after a 2-week treatment with either glargine or detemir once daily (randomized, double-blind, crossover study).

Research design and methods: Plasma glucose was clamped at 100 mg/dl for 24 h after subcutaneous injection of 0.35 unit/kg. The primary end point was end of action (time at which plasma glucose was >150 mg/dl).

Results: With glargine, plasma glucose remained at 103 +/- 3.6 mg/dl up to 24 h, and all subjects completed the study. Plasma glucose increased progressively after 16 h with detemir, and only eight subjects (33%) completed the study with plasma glucose <180 mg/dl. Glucose infusion rate (GIR) was similar with detemir and glargine for 12 h, after which it decreased more rapidly with detemir (P < 0.001). Estimated total insulin activity (GIR area under the curve [AUC](0-end of GIR)) was 1,412 +/- 662 and 915 +/- 225 mg/kg (glargine vs. detemir, P < 0.05), with median time of end of action at 24 and 17.5 h (glargine vs. detemir, P < 0.001). The antilipolytic action of detemir was lower than that of glargine (AUC free fatty acids(0-24 h) 11 +/- 1.7 vs. 8 +/- 2.8 mmol/l, respectively, P < 0.001).

Conclusions: Detemir has effects similar to those of glargine during the initial 12 h after administration, but effects are lower during 12-24 h.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Area Under Curve
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / therapeutic use
  • Insulin / analogs & derivatives*
  • Insulin / pharmacokinetics
  • Insulin / therapeutic use
  • Insulin Detemir
  • Insulin Glargine
  • Insulin, Long-Acting
  • Male
  • Middle Aged

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Insulin, Long-Acting
  • Insulin Glargine
  • Insulin Detemir