Ultrarapid lispro lowers postprandial glucose and more closely matches normal physiological glucose response compared to other rapid insulin analogues: A phase 1 randomized, crossover study

Aims To compare the pharmacokinetic (PK) and glucodynamic (GD) characteristics of ultra rapid lispro (URLi; Eli Lilly and Company, Indianapolis, Indiana), Fiasp (R) (Novo Nordisk, Bagsvaerd, Denmark), Humalog (R) (Eli Lilly and Company) and NovoRapid (R) (Novo Nordisk), in patients with type 1 diabetes (T1D). Materials and Methods This was a randomized, double-blind, four-period, crossover study, conducted in 68 patients with T1D. Patients received the same individualized subcutaneous dose of each study drug immediately prior to a liquid test meal. For comparison, 12 healthy subjects received the same test meal. Results URLi had a significantly faster insulin absorption compared to the other insulins tested. Early half-maximal drug concentration was reached 13 minutes after administration of URLi, which was 6 minutes faster than Fiasp, 13 minutes faster than Humalog, and 14 minutes faster than NovoRapid (allP <0.0001). Early insulin exposure was significantly greater and late insulin exposure was reduced after URLi compared to the other insulins. URLi achieved the greatest numerical reduction in postprandial glucose (PPG) at 2 hours post-meal (7 mg/dL vs Fiasp) and was significantly different from Humalog (21 mg/dL) and Novo Rapid (29 mg/dL). Additionally, glucose excursions over the first 3 hours post-meal with URLi were comparable to those in healthy subjects. Conclusions URLi demonstrated the fastest insulin absorption and the greatest numeric PPG-lowering effect compared to the other insulins tested. URLi more closely matched the early physiological glucose control observed in healthy subjects.