title: 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.
abstract: 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.
  
  
  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.
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany reinhard.becker@sanofi.com.
authors.forename: Reinhard H A
authors.initials: RH
authors.lastname: Becker
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany.
authors.forename: Raphael
authors.initials: R
authors.lastname: Dahmen
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Bergmann
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Lehmann
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jax
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Heise
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine