1112-P: Ultra Rapid Lispro (URLi) Lowers Postprandial Glucose (PPG) and More Closely Matches Normal Physiological Glucose Response Compared with Other Rapid Insulin Analogs

Abstract

URLi is a novel prandial insulin lispro formulation developed to more closely match physiological insulin secretion. This randomized, double-blind, 4-period, crossover study, compared the PK and glucodynamics (GD) of URLi, Humalog® (HL), NovoRapid® (NR) and Fiasp® (FA) after a test meal in 68 adults with T1D, after single individualized SC dose. Twelve healthy subjects provided the “normal” insulin secretory and glucose response to the test meal. URLi had the fastest insulin absorption: early half maximal drug concentration was reached at 13 min (URLi), 19 min (FA), 25 min (HL), and 27 min (NR) (p<0.05, URLi vs. other insulins). Early insulin exposure increased more with URLi: 1.5-fold vs. FA, 5-fold vs. HL, and 5-fold vs. NR in the first 15 min after dose (all p<0.002). Late insulin exposure (2h to 7h) was reduced more with URLi: 37% vs. FA, 30% vs. HL, and 45% vs. NR (all p<0.001). URLi significantly reduced PPG excursions up to 4h vs. HL and NR (Figure) and URLi’s PPG profile more closely matched that of healthy subjects in the first 2 hours post-meal (Figure). Hypoglycemic events were similar between insulins during the test meal. URLi demonstrated the fastest insulin absorption and the lowest PPG compared to all insulins tested and more closely matched the normal physiological profile of nondiabetic subjects. Disclosure 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. H. Linnebjerg: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. D. Cao: 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. E. Zijlstra: Speaker's Bureau; Self; Novo Nordisk A/S. C. Kapitza: Research Support; Self; ADOCIA, Biocon, Boehringer Ingelheim Pharmaceuticals, Inc., Dance Biopharm Holdings Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, MedImmune, Mylan, Nestlé, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Sanofi-Aventis, Wockhardt, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. J.M. Bue-Valleskey: Employee; Self; Eli Lilly and Company. Q. Zhang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. 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