Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Pharmacodynamic/pharmacokinetic (PK/PD) profile of new insulin glargine 300U/ml (Gla-300) during euglycaemic clamp in patients with type 1 diabetes. (#331)

Christoph Kapitza 1 , Thomas Jax 1 , Irene Nowotny 2 , Stephen Twigg 3 , Lenore Teichert 2 , Karin Bergman 2 , Raphael Dahmen 2 , Anne Lehmann 2 , Ronald Schmidt 2 , Reinhard Becker 2
  1. Profil, Neuss, Germany
  2. Sanofi, Frankfurt, Germany
  3. Dept of Endocrinology, Royal Prince Alfred Hospital and Sydney Medical School, The University of Sydney, NSW, Australia

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.

  1. Tillner et al. Diabetes 2013 62:Suppl 1;A217-A364.
  2. Dahmen et al. Diabetes 2013 62:Suppl 1;A1-A98.
  3. Becker et al. ADA 74th Scientific Sessions, 13-17 June 2014, San Francisco, USA.