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

• Published in: Diabetes, obesity & metabolism Vol. 17; no. 3; pp. 254 - 260
• Main Authors: Shiramoto, M, Eto, T, Irie, S, Fukuzaki, A, Teichert, L, Tillner, J, Takahashi, Y, Koyama, M, Dahmen, R, Heise, T, Becker, R H A
• Format: Journal Article
• Language: English
• Published: Oxford Wiley Subscription Services, Inc 01-03-2015
• Subjects: Diabetes; Diabetes mellitus (insulin dependent); Dosage; Glucose; Glucose metabolism; Hemoglobin; Insulin; Pharmacodynamics; Pharmacokinetics; Studies
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.12415

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.