1107-P: Ultra Rapid Lispro (URLi) Accelerates Insulin Lispro Absorption and Insulin Action vs. Humalog (Lispro) in Patients with T1D

Abstract

URLi is a novel prandial insulin lispro formulation developed to more closely match physiological insulin secretion. This randomized, double-blind, 2 period, crossover, 10 h euglycemic clamp study assessed PK and glucodynamics after one 15U SC dose of URLi and lispro in 41 patients with T1D (mean ± SD age, 32.0 ± 6.8 y; duration of T1D, 17.7 ± 9.3 y; HbA1c, 7.2 ± 0.6%; BMI, 24.8 ± 2.4 kg/m2). After dosing URLi, onset of insulin lispro appearance in the serum was faster (1.3 vs. 6.8 min; p<0.0001) and early insulin lispro exposure was greater (7.2 fold in the first 15 min and 2.7-fold in the first 30 min; both p<0.0001) vs. lispro. The duration of exposure, when serum lispro levels fell below the limit of quantification, was 74 min shorter with URLi (p<0.0001). Onset of insulin action was also faster (20 vs. 31 min; p=0.0007) and early action was increased 2.8 fold (p<0.001) in the first 30 min for URLi vs. lispro. Late insulin action (glucose infused from 4 h to end of the clamp) was reduced by 54% (p<0.0001) and duration of action was 43.6 min shorter with URLi (Figure). Total insulin lispro exposure and glucose infused during the clamp did not differ and tolerability was similar between URLi vs. lispro. In patients with T1D, URLi accelerated insulin absorption with a reduced late exposure and overall shorter duration vs. lispro, resulting in faster onset of insulin action and reduced late insulin action. Disclosure H. Linnebjerg: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Q. Zhang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; 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. D.E. Coutant: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. U. Hoevelmann: None. L. Plum-Moerschel: None. T. Herbrand: None. J. Leohr: Employee; Spouse/Partner; Accenture. Employee; Self; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Accenture. Stock/Shareholder; Self; Eli Lilly and Company. Funding Eli Lilly and Company