Comparison of the pharmacokinetic and pharmacodynamic profiles of insulin degludec and insulin glargine

Expert Opin Drug Metab Toxicol. 2015;11(8):1193-201. doi: 10.1517/17425255.2015.1058779. Epub 2015 Jun 18.


Objectives: A medical need remains for a once-daily insulin with 24-h basal coverage in all patients. We characterize the steady-state (SS) pharmacokinetic/pharmacodynamic properties of insulin degludec (IDeg) versus insulin glargine (IGlar).

Research design and methods: In this controlled, single-center study, 66 type 1 diabetes patients were randomized to two 8-day periods of once-daily IDeg or IGlar at 0.4, 0.6 or 0.8 U/kg. At SS, subjects underwent a 42-h euglycemic glucose clamp (5.5 mmol/l; 100 mg/dl). Glucose infusion rate (GIR), distribution of GIR and half-life were assessed.

Results: Mean 24-h GIR profiles were flatter and more stable for all doses of IDeg versus IGlar. The evenly distributed glucose-lowering effect of IDeg was confirmed by the AUCGIR across one dosing interval, as each of the four 6-h intervals across one dosing interval contributed ∼ 25% of the AUCGIR,τ,SS. IGlar was most effective during the first 12 - 18 h after dosing. At SS, the half-life was 25.4 (IDeg) versus 12.1 h (IGlar). No safety concerns were identified for IDeg or IGlar.

Conclusion: IDeg has a longer half-life (> 25 h) than IGlar. Exposure and glucose-lowering effects are more stable and evenly distributed across one dosing interval for IDeg versus IGlar (Clinical identifier: NCT01114542).

Keywords: euglycemic glucose clamp; insulin degludec; insulin glargine; pharmacodynamics; pharmacokinetics; type 1 diabetes.

Publication types

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

MeSH terms

  • Adult
  • Area Under Curve
  • Blood Glucose / drug effects
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Double-Blind Method
  • Female
  • Glucose Clamp Technique
  • Half-Life
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / pharmacology
  • Insulin Glargine / administration & dosage*
  • Insulin Glargine / pharmacokinetics
  • Insulin Glargine / pharmacology
  • Insulin, Long-Acting / administration & dosage*
  • Insulin, Long-Acting / pharmacokinetics
  • Insulin, Long-Acting / pharmacology
  • Male
  • Middle Aged
  • Young Adult


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

Associated data