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

• Published in: Diabetes, obesity & metabolism Vol. 16; no. 9; pp. 873 - 876
• Main Authors: Steinstraesser, A., Schmidt, R., Bergmann, K., Dahmen, R., Becker, R. H. A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-09-2014; Wiley Subscription Services, Inc
• Subjects: Blood Glucose - drug effects; Blood Glucose - metabolism; Cross-Over Studies; Diabetes; Diabetes mellitus (insulin dependent); 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; insulin analogues; Insulin Glargine - administration & dosage; Insulin Glargine - blood; Insulin Glargine - pharmacokinetics; Liquid chromatography; Mass spectroscopy; Metabolism; Metabolites; Pharmacokinetics; Research Letters; Treatment Outcome; type 1 diabetes; pharmacokinetics; insulin analogues; type 1 diabetes
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.12283

Insulin glargine is processed in vivo into soluble 21A‐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.