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.

Keywords: insulin analogues; pharmacokinetics; type 1 diabetes.

Figure 1

Cumulative exposure to M0, M1 and M2 in individual participants at steady state, assessed as the area under the insulin concentration time curve from time zero to 36 h post-dosing (M0-M1-M2-AUC_0–36), by treatment group.

Figure 2

Median trough levels of M1 with an exponential regression of the data. Vertical dashed lines denote the time at which 90% of the plateau is achieved. For convenience, in this figure, the two Gla-100 reference groups are combined as a weighted average of the medians.