Single-dose new insulin glargine 300U/ml provides prolonged, stable glycaemic control in Japanese and European people with type 1 diabetes

Abstract

Aims: Two single-dose studies were conducted in Japan and Europe to compare the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of new insulin glargine 300U/ml (Gla-300) and insulin glargine 100U/ml (Gla-100) in people with type 1 diabetes mellitus. Methods: In two double-blind, randomized, crossover studies, 18 Japanese participants (aged 20-65years) and 24 European participants (aged 18-65years) with glycated haemoglobin levels ≤9.0% (≤75mmol/mol) received single subcutaneous doses of Gla-300, 0.4, 0.6 and 0.9U/kg (0.9U/kg in the European study only), and Gla-100, 0.4U/kg. A 36-h euglycaemic clamp procedure was performed after each dosing. Results: The serum insulin glargine concentration (INS) and glucose infusion rate (GIR) developed more gradually into more constant and prolonged profiles with Gla-300 than with Gla-100. In support of this, the times to 50% of glargine exposure and insulin activity were longer for all Gla-300 doses than for Gla-100 during the 36-h clamp period, indicating a more evenly distributed exposure and metabolic effect beyond 24h. Exposure to insulin glargine and glucose utilization were lower with the 0.4 and 0.6U/ml Gla-300 doses in both studies compared with the 0.4U/ml Gla-100 dose. Glucose-lowering activity was detected for up to 36h with all doses of Gla-300. Conclusions: Single-dose injections of Gla-300 present more constant and prolonged PK and PD profiles compared with Gla-100, maintaining blood glucose control for up to 36h in euglycaemic clamp settings in Japanese and European participants with type 1 diabetes.