The new insulin glargine 300 U/ml (Gla-300) was examined in three protocols for its PK and PD properties, and compared with insulin glargine 100U/ml (Gla-100).
Study 1 (n=24): single SC doses of Gla-300 (0.4, 0.6, 0.9U/kg) and Gla-100 (0.4U/kg). Mean profiles of serum insulin concentrations (INS), BG, and smoothed (LOESS factor = 0.06) body-weight-standardized glucose infusion rate (GIR) were different.1 Gla-300 showed smoother profiles with less fluctuation in individual GIRs whilst still providing full BG control at clamp end (36h).
Study 2 (n=30): multiple SC doses of Gla-300 (0.4, 0.6U/kg QD) and Gla-100 (0.4U/kg QD) in an 8-day regimen.2 At steady state, exposure and activity of Gla-300 0.4 U/kg QD were more evenly distributed over 24- and 36 hours, presenting with stable, plateau-like INS- and GIR-profiles from dosing over 24h and a slow decline beyond, with activity until clamp end (36h). GIRmax was lower, fluctuation of individual GIRs less and euglycaemia maintained longer with 0.4 U/kg Gla-300 (32h) and 0.6 U/kg Gla-300 (34h) than with 0.4 U/kg Gla-100 (29h).
Study 3 (n=50): replicate 24h euglycaemic clamps in steady state after 6 QD administrations of Gla-300 (0.4U/kg) each.3 Cumulative exposure and activity developed linearly over 24h, there was low fluctuation in INS over time with mean excursion from the average INS within 24h of 3.3 µU/mL.Within-day SWING and peak-to-trough fluctuation were <1. Between-day, within subject exposure variability was 17.4 % (CV%, 90% CI 14.9;21.1) at a between-subject CV% of 34.8 % (90% CI 28.8;43.4).
In summary, this data which has been published in abstract form only, shows that the new insulin glargine 300 U/ml (Gla-300) confers straighter, flatter and more extended PK/PD profiles with prolonged tight blood glucose (BG) control, than insulin glargine 100U/ml (Gla-100), and provides evenly distributed 24h coverage and beyond, at a clinically relevant dose of 0.4 U/kg.
Funding: Sanofi funded all studies and abstract editorial support.