Investigational new insulin glargine 300 U/ml has the same metabolism as insulin glargine 100 U/ml

Diabetes Obes Metab. 2014 Sep;16(9):873-6. doi: 10.1111/dom.12283. Epub 2014 Mar 24.


Insulin glargine is processed in vivo into soluble 21(A) -Gly-human insulin (M1), the principal moiety responsible for metabolic effects, and subsequently into M2. This sub-study compared metabolism and metabolite pharmacokinetic (PK) profiles of investigational new insulin glargine U300 (Gla-300) with insulin glargine 100 U/ml (Gla-100, Lantus®, Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany) in people with type 1 diabetes. Participants received 0.4 (n = 18) or 0.6 U/kg Gla-300 (n = 12), and 0.4 U/kg Gla-100 (n = 30) once daily in randomized order for 8 days prior to a 36-h euglycaemic clamp. Metabolites were quantified using immunoaffinity enrichment and liquid chromatography tandem mass spectrometry (LC-MS/MS). Glargine metabolism was the same regardless of Gla-100 or Gla-300 administration; M1 was confirmed as the principal active moiety circulating in blood. Steady state concentrations of M1 were achieved after 2 days for Gla-100, and 4 days for Gla-300. Steady state M1 values defined prolonged and even flatter PK profiles after Gla-300 administration compared with M1 profiles after Gla-100.

Keywords: insulin analogues; pharmacokinetics; type 1 diabetes.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Double-Blind Method
  • Drugs, Investigational / administration & dosage
  • Drugs, Investigational / pharmacokinetics*
  • Glucose Clamp Technique
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / pharmacokinetics*
  • Insulin Glargine / administration & dosage
  • Insulin Glargine / blood
  • Insulin Glargine / pharmacokinetics*
  • Treatment Outcome


  • Blood Glucose
  • Drugs, Investigational
  • Hypoglycemic Agents
  • Insulin Glargine