The first biosimilar of ultra-rapid insulin lispro: results of a double-blind randomised clamp study

Introduction . Over the years, insulin therapy has remained an important component of the complex treatment of patients with diabetes mellitus. Ultra-rapid insulin lispro is a DNA recombinant analogue of human insulin, which has a pharmacokinetic (PK) profile that is as close as possible to the endogenous insulin secretion profile, which ensures effective control of postprandial glycaemia. The development of the ultra-rapid insulin lispro biosimilar will expand the range and increase the availability of modern and safe insulin analogues for diabetic patients in Russia. Aim . To compare the PK and pharmacodynamic (PD) profiles of GP40261 (ultra-rapid insulin lispro biosimilar) and the reference Lyumjev® in healthy volunteers. Materials and methods . This was a double-blind, randomised, comparative, crossover study in healthy volunteers who were administered either the test or reference ultra-rapid insulin lispro formulation as a single dose of 0.3 IU/kg. The hyperinsulinaemic euglycaemic clamp technique was used to evaluate the pharmacokinetics and pharmacodynamics of the study products. In order to assess the biosimilarity of the products, 90% confidence intervals (CIs) were calculated for geometric mean ratios of the primary PK parameters AUCins.0-t and Cins.max. The PD parameters of the study drugs were evaluated based on the glucose infusion rate required to maintain the target glycaemic level during the clamp. Results . The 90% CIs for the geometric mean ratios of the primary PK parameters for the test and reference products were 89.41-94.55% for AUCins.0-t and 82.74-92.92% for Cins.max, which complies with the established acceptance limits of 80-125% for both parameters. The study products were also found to have comparable PD profiles of their active substances. Conclusion . This clinical study has demonstrated that GP40261 and the reference ultra-rapid insulin lispro are biosimilar and have a comparable safety profile.