Equipotency of insulin glargine andregular human insulin on glucose disposal in healthy subjectsfollowing intravenous infusion

Abstract. The absolute glucose disposal of insulin glargine (Lantus)was compared to that of regular human insulin in healthysubjects (n=20) using the euglycaemic clamp technique in asingle-dose, double-blind, randomized, two-way crossover design.Subjects received 30-minute intravenous infusions of insulinglargine (0.1 IU/kg) or human insulin (0.1 IU/kg) and a 20%glucose solution infused at a variable rate to maintaineuglycaemia at the subjects baseline glucose level. At equalbaseline blood glucose levels (4.42 mmol/l [range, 4.00–5.16mmol/l] and 4.42 mmol/l [range, 4.01–4.94 mmol/l],respectively), the area under the glucose infusion rate (GIR)time curves from 0–6 hours (AUC_(0–6h))was within the bioequivalence range (insulin glargine, 663.92mg/kg; human insulin, 734.85 mg/kg). Both the time to maximumGIR and the suppression of serum C-peptide were similar withinsulin glargine and human insulin. The resulting maximum seruminsulin concentrations (C_max) were 151.16µIU/ml and 202.23 µIU/ml, and the time toC_max (T_max) was 30minutes (the duration of the infusion). The observed differencesin the C_max (the mean value for insulinglargine was about 25% lower than that of human insulin) couldbe explained by lower cross-reactivity of insulin glargine inthe human insulin radioimmunoassay. The employed intravenousroute, though definitely not the intended clinical use ofinsulin glargine, provided the clinical evidence in healthysubjects that on a molar basis insulin glargine is equipotent toregular human insulin regarding glucose disposal.