Objective: To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of a new insulin glargine comprising 300 units · mL(-1) (Gla-300), compared with insulin glargine 100 units · mL(-1) (Gla-100) at steady state in people with type 1 diabetes.
Research design and methods: A randomized, double-blind, crossover study (N = 30) was conducted, applying the euglycemic clamp technique over a period of 36 h. In this multiple-dose to steady-state study, participants received once-daily subcutaneous administrations of either 0.4 (cohort 1) or 0.6 units · kg(-1) (cohort 2) Gla-300 for 8 days in one treatment period and 0.4 units · kg(-1) Gla-100 for 8 days in the other. Here we focus on the results of a direct comparison between 0.4 units · kg(-1) of each treatment. PK and PD assessments performed on the last treatment day included serum insulin measurements using a radioimmunoassay and the automated euglycemic glucose clamp technique over 36 h.
Results: At steady state, insulin concentration (INS) and glucose infusion rate (GIR) profiles of Gla-300 were more constant and more evenly distributed over 24 h compared with those of Gla-100 and lasted longer, as supported by the later time (∼ 3 h) to 50% of the area under the serum INS and GIR time curves from time zero to 36 h post dosing. Tight blood glucose control (≤ 105 mg · dL(-1)) was maintained for approximately 5 h longer (median of 30 h) with Gla-300 compared with Gla-100.
Conclusions: Gla-300 provides more even steady-state PK and PD profiles and a longer duration of action than Gla-100, extending blood glucose control well beyond 24 h.
Trial registration: ClinicalTrials.gov NCT01349855.
© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.