Steady state is reached within 2–3 days of once‐daily administration of degludec, a basal insulin with an ultralong duration of action1. (24th March 2015)

• Record Type: Journal Article
• Authors: Heise, Tim; Korsatko, Stefan; Nosek, Leszek; Coester, Hans Veit; Deller, Sigrid; Roepstorff, Carsten; Segel, Stine; Kapur, Rahul; Haahr, Hanne; Hompesch, Marcus
• Is Part Of: Journal of diabetes. Volume 8:Number 1(2016:Jan.)
• Page Start: 132
• Page End: 138
• Publication Date: 2015-03-24
• Subjects: basal insulin -- diabetes -- pharmacokinetics -- steady state; 基础胰岛素 -- 糖尿病 -- 药物代谢动力学 -- 稳态; Diabetes -- Periodicals; 618.3646005
• DOI: 10.1111/1753-0407.12266
• Languages: English
• ISSNs: 1753-0393

Abstract

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.