Steady state is reached within 2-3 days of once-daily administration of degludec, a basal insulin with an ultralong duration of action

J Diabetes. 2016 Jan;8(1):132-8. doi: 10.1111/1753-0407.12266. Epub 2015 Mar 24.

Abstract

Background: Various factors influence the pharmacokinetic and pharmacodynamic properties of insulin analogs. The aim of the present study was to determine time to steady state of insulin degludec (IDeg), a basal insulin analog with an ultralong duration of action, after once-daily subcutaneous administration in subjects of varying age, diabetes type, and ethnicity.

Methods: Time to steady state was analyzed in 195 subjects across five Phase I randomized single-center double-blind studies: three in subjects with type 1 diabetes (T1DM), including one in elderly subjects, and two in subjects with type 2 diabetes (T2DM), including one with African American and Hispanic/Latino subpopulations. Subjects received once-daily IDeg (100 U/mL, s.c.) at doses of 0.4-0.8 U/kg for 6-12 days. Time to clinical steady state was measured from first dose until the serum IDeg trough concentration exceeded 90% of the final plateau level. The IDeg concentrations were log-transformed and analyzed using a mixed-effects model with time from first dose and dose level (where applicable) as fixed effects, and subject as a random effect.

Results: Steady state serum IDeg concentrations were reached after 2-3 days in all subjects. In trials with multiple dose levels, time to steady state was independent of dose level in T1DM (P = 0.51) and T2DM (P = 0.75).

Conclusions: Serum IDeg concentrations reached steady state within 2-3 days of once-daily subcutaneous administration in all subjects with T1DM or T2DM, including elderly and African American and Hispanic/Latino subjects. At steady state, serum IDeg concentrations were unchanged from day to day.

Keywords: basal insulin; diabetes; pharmacokinetics; steady state; 基础胰岛素; 稳态; 糖尿病; 药物代谢动力学.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • African Americans
  • Aged
  • Area Under Curve
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / ethnology
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / metabolism*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Hispanic Americans
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacokinetics*
  • Injections, Subcutaneous
  • Insulin, Long-Acting / administration & dosage
  • Insulin, Long-Acting / pharmacokinetics*
  • Male
  • Middle Aged
  • Time Factors
  • Young Adult

Substances

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