title: Single-dose new insulin glargine 300 U/ml provides prolonged, stable glycaemic control in Japanese and European people with type 1 diabetes.
abstract: OBJECTIVE
  Two single-dose studies were conducted in Japan and Europe to compare the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of new insulin glargine 300 U/ml (Gla-300) and insulin glargine 100 U/ml (Gla-100) in people with type 1 diabetes mellitus.
  
  
  METHODS
  In two double-blind, randomized, crossover studies, 18 Japanese participants (aged 20-65 years) and 24 European participants (aged 18-65 years) with glycated haemoglobin levels ≤9.0% (≤75 mmol/mol) received single subcutaneous doses of Gla-300, 0.4, 0.6 and 0.9 U/kg (0.9 U/kg in the European study only), and Gla-100, 0.4 U/kg. A 36-h euglycaemic clamp procedure was performed after each dosing.
  
  
  RESULTS
  The serum insulin glargine concentration (INS) and glucose infusion rate (GIR) developed more gradually into more constant and prolonged profiles with Gla-300 than with Gla-100. In support of this, the times to 50% of glargine exposure and insulin activity were longer for all Gla-300 doses than for Gla-100 during the 36-h clamp period, indicating a more evenly distributed exposure and metabolic effect beyond 24 h. Exposure to insulin glargine and glucose utilization were lower with the 0.4 and 0.6 U/ml Gla-300 doses in both studies compared with the 0.4 U/ml Gla-100 dose. Glucose-lowering activity was detected for up to 36 h with all doses of Gla-300.
  
  
  CONCLUSIONS
  Single-dose injections of Gla-300 present more constant and prolonged PK and PD profiles compared with Gla-100, maintaining blood glucose control for up to 36 h in euglycaemic clamp settings in Japanese and European participants with type 1 diabetes.
authors.affiliation: Hakata Clinic, LTA Clinical Pharmacology Center, Fukuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shiramoto
authors.forename: T
authors.initials: T
authors.lastname: Eto
authors.forename: S
authors.initials: S
authors.lastname: Irie
authors.forename: A
authors.initials: A
authors.lastname: Fukuzaki
authors.forename: L
authors.initials: L
authors.lastname: Teichert
authors.forename: J
authors.initials: J
authors.lastname: Tillner
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.forename: M
authors.initials: M
authors.lastname: Koyama
authors.forename: R
authors.initials: R
authors.lastname: Dahmen
authors.forename: T
authors.initials: T
authors.lastname: Heise
authors.forename: R H A
authors.initials: RH
authors.lastname: Becker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D015309:Glucose Clamp Technique / Q000379:methods; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055104:Infusions, Subcutaneous / Q000379:methods; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D044465:White People; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting
keywords: insulin analogues; pharmacodynamics; pharmacokinetics; type 1 diabetes