Unlocking the Potential of LAPSInsulin115: A Comprehensive Review of a Novel Ultra-Long-Acting Insulin Analogue

The primary objective of the research was to evaluate a new type of insulin analogue, referred to as LAPSInsulin115, through a thorough pre-clinical examination. The study involved a comparison of its pharmacokinetic and pharmacodynamic properties with other insulins in genetically diabetic mice. Furthermore, the insulin’s signaling in the main target organs was examined in wild-type male Wistar rats after a single subcutaneous injection, using Western blot analysis.

In addition to this, the study also included in vitro tests to assess the transendothelial transport, insulin receptor interaction, and the mitogenic and metabolic characteristics of LAPSInsulin115. The long-term effects and potential for target cell desensitization were also studied through an in vitro desensitization/resensitization model.

The results indicated that LAPSInsulin115, a Fc-conjugated insulin derivative, demonstrated a significantly extended pharmacokinetic and pharmacodynamic profile in rodents. Even with a molecular weight of 59 kDa, it was able to cross the vascular endothelial barrier and activate insulin signaling in the rat's primary target tissues. Although LAPSInsulin115 had a slower onset of action due to lower insulin receptor affinity, it showed comparable metabolic potency over time and did not exhibit increased mitogenic activity compared to regular insulin. Notably, it did not lead to irreversible desensitization of target cells under chronic exposure conditions, likely due to less pronounced insulin receptor downregulation.

In conclusion, LAPSInsulin115 has a distinctive profile both in vivo and in vitro, positioning it as a promising candidate for a weekly insulin analogue.