New Insulin Glargine 300 Units.mL-1 Provides a More Even Activity Profile and Prolonged Glycemic Control at Steady State Compared With Insulin Glargine 100 Units.mL-1

OBJECTIVETo characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of a new insulin glargine comprising 300 unitsmL(-1) (Gla-300), compared with insulin glargine 100 unitsmL(-1) (Gla-100) at steady state in people with type 1 diabetes.RESEARCH DESIGN AND METHODSA 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 unitskg(-1) (cohort 2) Gla-300 for 8 days in one treatment period and 0.4 unitskg(-1) Gla-100 for 8 days in the other. Here we focus on the results of a direct comparison between 0.4 unitskg(-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.RESULTSAt 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 (approximate to 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 mgdL(-1)) was maintained for approximately 5 h longer (median of 30 h) with Gla-300 compared with Gla-100.CONCLUSIONSGla-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.