While first generation prandial insulins have a significantly faster onset of action compared to regular human insulin, a further left-shift in the time-action profile of prandial insulins might help to improve postprandial blood glucose control even more. Ultra-rapid insulin lispro (URLi) was developed to more closely match physiological insulin secretion by adding two new excipients: a micro-dose of treprostinil causing local vasodilation and citrate enhancing local vascular permeability.
The presentation will summarise the currently available pharmacological and clinical trials with URLi.
In comparison with insulin lispro (LIS), URLi showed a clear left-shift in the pharmacokinetic and pharmacodynamic profile with a faster onset of exposure and action, higher early and less late exposure and action. The faster absorption of URLi was confirmed in a comparative trial versus both conventional insulin aspart (ASP) and faster insulin aspart (FIA). The faster onset and offset of URLi led to improved post-prandial glucose (PPG) concentrations versus LIS, ASP and (non-significantly) versus FIA. Of note, URLi’s PPG profile more closely matched that of healthy subjects in the first 2-3 hours post-meal. Improvements in PPGs were also observed in larger clinical phase 3 trials vs. LIS.
URLi shows the fastest insulin absorption and shortest exposure duration compared to LIS, ASP and FIA leading to greater glucose lowering effects with statistically significant improvements in PPG excursions vs. LIS and ASP.