Morning administration of 0.4U/kg/day insulin glargine 300U/mL provides less fluctuating 24-hour pharmacodynamics and more even pharmacokinetic profiles compared with insulin degludec 100U/mL in type 1 diabetes

Diabetes Metab. 2018 Feb;44(1):15-21. doi: 10.1016/j.diabet.2017.10.001. Epub 2017 Nov 16.


Aim: To compare steady state pharmacodynamic and pharmacokinetic profiles of insulin glargine 300U/mL (Gla-300) with insulin degludec 100U/mL (Deg-100) in people with type 1 diabetes.

Methods: This single-centre, randomized, double-blind crossover euglycaemic clamp study included two parallel cohorts with fixed once-daily morning dose regimens. For both insulins participants received 0.4 (n=24) or 0.6U/kg/day (n=24), before breakfast, for 8 days prior to the clamp. The main endpoint was within-day variability (fluctuation) of the smoothed glucose infusion rate (GIR) over 24 hours (GIR-smFL0-24).

Results: Gla-300 provided 20% less fluctuation of steady state glucose infusion rate profiles than Deg-100 over 24 hours at 0.4U/kg/day (GIR-smFL0-24 treatment ratio 0.80 [90% confidence interval: 0.66 to 0.96], P=0.047), while at the dose of 0.6U/kg/day the difference between insulins was not statistically significant (treatment ratio 0.96 [0.83 to 1.11], P=0.603). Serum insulin concentrations appeared more evenly distributed with both dose levels of Gla-300 versus the same doses of Deg-100, as assessed by relative 6-hour fractions of the area under the curve within 24 hours. Both insulins provided exposure and activity until 30 hours (end of clamp).

Conclusion: Gla-300 provides less fluctuating steady state pharmacodynamic profiles (i.e. lower within-day variability) and more evenly distributed pharmacokinetic profiles, compared with Deg-100 in a once-daily morning dosing regimen of 0.4U/kg/day.

Keywords: Insulin degludec; Insulin glargine; Pharmacodynamic; Pharmacokinetic; Type 1 diabetes.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Glargine / administration & dosage
  • Insulin Glargine / pharmacokinetics
  • Insulin Glargine / therapeutic use*
  • Insulin, Long-Acting / administration & dosage
  • Insulin, Long-Acting / pharmacokinetics
  • Insulin, Long-Acting / therapeutic use*
  • Male
  • Middle Aged
  • Young Adult


  • Hypoglycemic Agents
  • Insulin, Long-Acting
  • Insulin Glargine
  • insulin degludec