Low within- and between-day variability in exposure to new insulin glargine 300 U/ml

Diabetes Obes Metab. 2015 Mar;17(3):261-7. doi: 10.1111/dom.12416. Epub 2015 Jan 7.


Aims: To characterize the variability in exposure and metabolic effect of insulin glargine 300 U/ml (Gla-300) at steady state in people with type 1 diabetes (T1DM).

Methods: A total of 50 participants with T1DM underwent two 24-h euglycaemic clamps in steady-state conditions after six once-daily administrations of 0.4 U/kg Gla-300 in a double-blind, randomized, two-treatment, two-period, crossover clamp study. Participants were randomized to receive Gla-300 as a standard cartridge formulation in the first treatment period, and as a formulation with enhanced stability through polysorbate-20 addition in the second treatment period, or vice versa. This design allowed the assessment of bioequivalence between formulations and, subsequently, within- and between-day variability.

Results: The cumulative exposure and effect of Gla-300 developed linearly over 24 h, and were evenly distributed across 6- and 12-h intervals. Diurnal fluctuation in exposure (within-day variability) was low; the peak-to-trough ratio of insulin concentration profiles was <2, and both the swing and peak-to-trough fluctuation were <1. Day-to-day reproducibility of exposure was high: the between-day within-subject coefficients of variation for total systemic exposure (area under the serum insulin glargine concentration time curve from time 0 to 24 h after dosing) and maximum insulin concentration were 17.4% [95% confidence interval (CI) 15-21] and 33.4% (95% CI 28-41), respectively. Reproducibility of the metabolic effect was lower than that of exposure.

Conclusions: Gla-300 provides predictable, evenly distributed 24-h coverage as a result of low fluctuation and high reproducibility in insulin exposure, and appears suitable for effective basal insulin use.

Keywords: insulin glargine; pharmacokinetics; type 1 diabetes.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Glucose Clamp Technique / methods
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / pharmacokinetics
  • Insulin Glargine
  • Insulin, Long-Acting / administration & dosage*
  • Insulin, Long-Acting / blood
  • Insulin, Long-Acting / pharmacokinetics
  • Male
  • Middle Aged
  • Reproducibility of Results
  • Therapeutic Equivalency
  • Young Adult


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