title: Investigational new insulin glargine 300 U/ml has the same metabolism as insulin glargine 100 U/ml.
abstract: 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.
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Steinstraesser
authors.forename: R
authors.initials: R
authors.lastname: Schmidt
authors.forename: K
authors.initials: K
authors.lastname: Bergmann
authors.forename: R
authors.initials: R
authors.lastname: Dahmen
authors.forename: R H A
authors.initials: RH
authors.lastname: Becker
mesh_terms: 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; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000069036:Insulin Glargine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D015507:Drugs, Investigational; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine
keywords: insulin analogues; pharmacokinetics; type 1 diabetes