Ultra Rapid Lispro (URLi) shows faster insulin absorption vs. Lispro during insulin pump (CSII) use in patients with T1D

Background:

Ultra Rapid Lispro (URLi; LY900014), a novel ultra-rapid mealtime insulin in Phase 3 development, is shown to reduce postprandial glucose after subcutaneous injection.

Materials and methods:

This study evaluated pharmacokinetics and pharmacodynamics (PD) of URLi via CSII. In a double-blind, randomised cross-over study, 24 adult patients with T1D received URLi or lispro (Humalog®) for 3 days. Mixed meal tolerance tests (MMTT) were conducted on Days 1 and 3 after catheter insertion using a standard single-wave bolus with the same, individualised insulin doses.

Results:

URLi showed faster insulin lispro absorption on Days 1 and 3 reducing time to early half-maximal drug concentration by 37% (-8.5 min) and 32% (-5.3 min) compared to lispro (both p < 0.0001). Area under the insulin lispro concentration time curve (AUC) for the first 15 min was > 50% higher than lispro after dosing with URLi on Days 1 and 3(p < 0.005). URLi reduced 1-hour postprandial glucose excursion of the MMTT by 45% on Day 1(p = NS) and 47% on Day 3(p = 0.059) compared with lispro.

URLi was associated with trends toward lower postprandial glucose excursion for the entire MMTT (57% and 20% reductions in ΔAUC[0 – 5h] on Days 1 and 3; both NS). The study was not powered for PD assessment which may contribute to the lack of statistical significance. No differences were seen in the number or severity of hypoglycaemic events or local tolerability between URLi and lispro.

Conclusion:

URLi demonstrated accelerated absorption and a trend toward improved postprandial glucose control in T1D subjects using CSII.