URLi is a novel prandial insulin lispro formulation developed to more closely match physiological insulin secretion. This phase 3, multicenter, treat-to-target, 26-week trial evaluated the efficacy and safety of URLi vs. lispro in patients with T2D. Primary endpoint was A1C change from baseline to week 26, with multiplicity adjusted objectives for PPG excursions (PPGE) with meal test. After 8-week lead-in to optimize basal insulin glargine or degludec and transfer to prandial lispro treatment, patients were randomized to double-blind URLi (n=336) or lispro (n=337) injected 0 to 2 minutes prior to meals. Patients could continue metformin and/or SGLT2 inhibitor.
Non-inferiority for primary endpoint was confirmed for URLi: estimated treatment difference (ETD) 0.06 [95% CI -0.05; 0.16], with mean change in A1C of -0.38% URLi and -0.43% lispro (Figure). Mean A1C at week 26 was 6.92% URLi and 6.86% lispro. URLi was superior to lispro in controlling 1- and 2-h PPGE with standardized meal test at week 26, with lower PPGE from 0.5-4 h with URLi (Figure). There were no significant treatment differences in rates of severe or overall hypoglycemia. Incidence of overall treatment-emergent adverse events was similar between treatments.
URLi in a basal-bolus regimen led to superior PPG control vs. lispro in patients with T2D.
T. Blevins: Research Support; Self; Amgen Inc., Gan and Lee Pharma, Lilly Diabetes, Mylan, Novo Nordisk Inc. Speaker's Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Lilly Diabetes, Sanofi US. Other Relationship; Self; Medtronic MiniMed, Inc. Q. Zhang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. J.P. Frias: Advisory Panel; Self; Becton, Dickinson and Company, Eli Lilly and Company, Gilead Sciences, Inc., Sanofi. Consultant; Self; Echosens, Genentech, Inc., Johnson & Johnson Diabetes Institute, Novo Nordisk Inc., Zafgen, Inc. Research Support; Self; AbbVie Inc., Akcea Therapeutics, Allergan, Amgen Inc., AstraZeneca, Bayer US, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Cirius Therapeutics, Elcelyx Therapeutics, Inc., Eli Lilly and Company, Enanta Pharmaceuticals, Inc., GENFIT, Intarcia Therapeutics, Inc., Intercept Pharmaceuticals, Inc., Ionis Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., NGM Biopharmaceuticals, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Oramed Pharmaceuticals, Pfizer Inc., Sanofi, TaiwanJ Pharmaceuticals Co., Ltd., Theracos, Inc. Speaker's Bureau; Self; Merck & Co., Inc., Sanofi. H. Jinnouchi: None. A.M. Chang: Employee; Self; Eli Lilly and Company.
Eli Lilly and Company
