Diabetologie und Stoffwechsel 2014; 9 - P116
DOI: 10.1055/s-0034-1374973

LY2605541 (LY) exhibits a Flatter Glucodynamic profile than insulin Glargine (GL) at steady state in subjects with Type 1 Diabetes (T1D)

L Morrow 1, M Hompesch 1, S Jacober 2, SL Choi 3, Y Qu 2, V Sinha 2, 4
  • 1Profil Institute for Clinical Research, Inc., Chula Vista, United States
  • 2Eli Lilly and Company, Indianapolis, United States
  • 3Eli Lilly and Company Lilly-NUS Centre for Pharmacology Pte, Ltd, Singapore, Singapore
  • 4Food and Drug Administration, Silver Spring, United States

Aim: The aim of this open-label, randomized Phase2 crossover substudy was to investigate the glucodynamic profile of LY, a novel basal insulin analog with prolonged duration of action, compared to GL.

Methods: 23 T1D patients underwent 24h Biostator-controlled euglycemic clamps after 8-wks treatment with GL or LY. Clinically titrated basal insulin doses (LY: 16 – 64U, GL: 19 – 60U) were administered the morning of the clamp. Locally weighted scatterplot smoothing (LOESS) function was applied to individual glucose infusion rate (GIR)-versus-time profiles in each treatment group and/or period. Mean LOESS fits of dose-normalized GIR-versus-time profiles were generated using LOESS fits from all subjects to calculate the mean LOESS fits of GIR for each time point.

Results: At baseline, mean (SD) BMI was 26.8 kg/m2± 4.2; mean A1C was 7.7%± 1.0. Endpoint dose (U/kg) was LY: 0.43 ± 0.13, GL: 0.42 ± 0.10. Mean GIR normalized to unit of insulin was less for LY than GL and persistent over 24h. The GIR profile for LY is consistent with a peak to trough fluctuation ratio < 1.5. Inter-subject GIR variability was LY: 0.67, GL: 0.53. Eight LY and 1 GL patients had minimal GIRs over 24h (defined as < 800 mg/kg), indicating optimal glucose control. Mean total glucose infused (GTOT(0 – 24); g/kg) was LY: 1.22 ± 0.82, GL: 1.90 ± 1.01, p < 0.01. Mean GTOT(0 – 6) (g/kg) was LY: 0.21 ± 0.22, GL: 0.41 ± 0.22, p < 0.01. Mean GTOT(18 – 24) (g/kg) was LY: 0.28 ± 0.18, GL: 0.35 ± 0.23, p = 0.20.

Conclusion: LY has a flatter profile than GL, with potentially more stable and predictable metabolic control. LY may have a novel mechanism of action as LY GTOT(0 – 24) is less than GL with similar glycemic control.

Presenter: Nanette Schloot