Fluctuation and reproducibility of exposure and effect of insulin glargine in healthy subjects

Aim: Low diurnal fluctuation and high day‐to‐day reproducibility in exposure and effect characterize beneficial basal insulin products. Two insulin glargine (LANTUS) formulations [without (R) or with polysorbate‐20 (T)], added to minimize unfolding of proteins and subsequent formation of fibril structures, were assessed for equivalence in exposure and effect, and aspects of fluctuation and reproducibility in time–concentration and time–action profiles. Methods: A dose of 0.4 U/kg was subcutaneously administered to 24 healthy subjects in a two‐sequence (R‐T‐R‐T or T‐R‐T‐R), randomized, four‐way crossover trial utilizing 30‐h Biostator‐based euglycaemic glucose clamps. Results: Identical serum insulin glargine concentration and time–action profiles established average, individual and population equivalence in insulin exposure and effect. Point estimates for 24‐h area under the curve for insulin (INS–AUC_{0–24 h}) and glucose infusion rates (GIR–AUC_{0–24 h}) were 97% [90% confidence interval (CI): 91–103%] and 100% (88–114%), respectively. Within‐subject variability (coefficient of variation) for INS–AUC_{0–24 h} and GIR–AUC_{0–24 h} were 19% (95% CI: 14–25%) and 34% (24–43%), respectively. The diurnal relative fluctuation of the serum insulin glargine concentration was 20% (95% CI: 19–21%). Conclusion: Insulin glargine in either formulation presents with a high day‐to‐day reproducibility of a uniform release after injection enabling an effective basal insulin supplementation.