Ultra fast-acting insulins in closed-loop systems
Afrezza – How to use it and when
FiAsp insulin – Evidence and experience in using it
Abstract
Background and Aims
In normal physiology, insulin is secreted very rapidly from the β‐cell in response to, and even in anticipation of a meal. Despite advances in insulin formulations, subcutaneously administered insulins have a delayed onset and a longer duration of action compared with endogenously secreted insulin. This fact makes it challenging for persons with diabetes to control their postprandial glucose after most meals, whether patients are treated with basal-bolus insulin, insulin pumps or closed loop systems.
Rapid‐acting insulin analogues — insulin aspart, insulin lispro and insulin glulisine — have faster absorption kinetics than regular human insulin and are in the western world the most common fast-acting insulin used. However, the problem with postprandial hyperglycemia remains a major problem.
Fast‐acting insulin aspart (FiAsp) is a formulation of insulin aspart with an improved pharmacological profile and greater early glucose‐lowering action compared with insulin aspart, thus having the potential to be advantageous in controlling the glucose.
Methods
Review of publiced clinical trials with FiAsp
Results
Efficacy of FiAsp compared to other rapid acting insulin analogs used in MDI, insulin pumps and closed loop systems will be presented together with clinical experience using FiAsp.
Conclusions
Based on the data presented, the need for further studies to maximize the potential of FiAsp will be discussed
How early is URLi (Ultra Rapid Lispro)?
Abstract
Background and Aims
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.
Methods
The presentation will summarise the currently available pharmacological and clinical trials with URLi.
Results
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.
Conclusions
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.