1100-P: Ultra Rapid Lispro (URLi) Accelerates Insulin Lispro Absorption and Insulin Action vs. Humalog (Lispro) in Patients with T2D
Authors: LEOHR JENNIFER , DELLVA MARY A. , COUTANT DAVID E. , LABELL ELIZABETH S. , REDDY SHOBHA , HEISE TIM , ANDERSEN GRIT , ZIJLSTRA ERIC , HERMANSKI LIDIA , NOSEK LESZEK , LINNEBJERG HELLE 
Published: June 2019

URLi is a novel prandial insulin lispro formulation developed to more closely match physiological insulin secretion. This randomized, double-blind, 2 period, crossover, 10 hour euglycemic clamp study assessed the pharmacokinetics, glucodynamics and tolerability of insulin lispro after a single 15U SC dose of URLi and lispro (Humalog®) in 38 patients with T2D (mean [±SD] age, 60.0 ± 7.9 years; duration of diabetes, 17.4 ± 7.65 years; HbA1c, 7.4 ± 0.80%; BMI, 30.0 ± 2.97 kg/m2).
After dosing URLi, onset of insulin lispro appearance in serum was faster (1.97 vs. 7.28 min; p&lt;0.0001). The time to early half maximal drug concentration was reduced by 10.9 min (p&lt;0.0001) with URLi (18.6 min) vs. lispro (29.6 min). This resulted in greater early insulin lispro exposure: 6.4 fold in the first 15 min and 2.9-fold in the first 30 min after injection vs. lispro (both p&lt;0.0001). Total exposure or time to maximum observed drug concentration did not differ between URLi and lispro.
The onset of insulin action was also faster (31.99 vs. 44.69 min; p&lt;0.0001) and early insulin action (as measured by glucose infusion rate) was increased by 4.3 fold (p&lt;0.0001) in the first 30 min of the clamp for URLi vs. lispro. Late insulin action (glucose infused from 4 hours to the end of the clamp) was reduced by 19% (p=0.0108) with URLi vs. lispro. The overall total glucose infused was 12% higher (p=0.0488) for URLi vs. lispro.
No differences were seen in tolerability between URLi and lispro.
In patients with T2D, URLi showed an accelerated insulin lispro absorption with a reduced late exposure and overall shorter duration vs. lispro resulting in faster onset of action and reduced late insulin action. This was the first study to investigate URLi in patients with T2D using a euglycemic clamp and results confirmed the faster PK and GD profile of URLi in this population.

Disclosure
J. Leohr: Employee; Spouse/Partner; Accenture. Employee; Self; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Accenture. Stock/Shareholder; Self; Eli Lilly and Company. M.A. Dellva: Employee; Self; Eli Lilly and Company. D.E. Coutant: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. E.S. LaBell: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company, Johnson & Johnson, Novartis AG. S. Reddy: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. T. Heise: Advisory Panel; Self; Mylan. Research Support; Self; ADOCIA, Boehringer Ingelheim International GmbH, Dance Biopharm Holdings Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Johnson & Johnson, MedImmune, Mylan, Nordic Bioscience, Novo Nordisk A/S, Pfizer Inc., Poxel, Saniona, Sanofi, Wockhardt, Zealand Pharma A/S. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S. G. Andersen: None. E. Zijlstra: Speaker's Bureau; Self; Novo Nordisk A/S. L. Hermanski: None. L. Nosek: None. H. Linnebjerg: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.

Funding
Eli Lilly and Company