108-LB: Ultrarapid Lispro (urli) Accelerates Insulin Lispro Absorption and Insulin Action Vs. Humalog (lispro) in Healthy Chinese Subjects

URLi is a novel insulin lispro formulation developed to more closely match physiological insulin secretion. This randomized, subject-blind, 3‑period, crossover, 10‑h euglycemic clamp study assessed the pharmacokinetics (PK), glucodynamics (GD) and tolerability after a 7U or 15U dose of URLi or 15U dose of Humalog in 15 healthy Chinese subjects. After a 15U dose, the early 50% tmax occurred 15.3 min (p<0.0001) sooner with URLi (8.1 min) vs. Humalog (23.4 min). This resulted in greater early insulin lispro exposure: 5.3-fold in the first 15 min and 2.8-fold in the first 30 min after injection vs. Humalog (both p<0.0001). Onset of insulin action was faster (8.57 vs. 17.1 min; p=0.0008) and early insulin action was increased by 2.5-fold (p=0.0002) in the first 30 min of the clamp for URLi vs. Humalog. Late insulin action (glucose infused from 4 h to the end of the clamp) was reduced by 56% (p=0.0076) and duration of action was 67.7 min shorter with URLi vs. Humalog. Total insulin lispro exposure and glucose infused during the clamp did not differ between URLi vs. Humalog. URLi is well tolerated in Chinese subjects. In healthy Chinese subjects, URLi accelerated insulin lispro absorption with a reduced late exposure vs. Humalog, resulting in faster onset of action, reduced late insulin action and overall shorter duration. This study confirmed the faster PK and GD profile of URLi in this population.View largeDownload slideView largeDownload slide DisclosureY. Yu: None. H. Tao: None. J. Leohr: None. E. S. Labell: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company, Johnson & Johnson, Novartis AG, Procter & Gamble Company. D. E. Coutant: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Eli Lilly and Company. H. Liu: None. C. Qian: None.