USA: Ultra-rapid lispro (URLi), a novel ultra-rapid mealtime insulin, showed accelerated insulin lispro absorption and greater reduction in postprandial glucose versus Humalog in type 2 diabetes patients, according to a recent study. The study was published in the journal Diabetes, Obesity and Metabolism.
Insulin lispro (Humalog) is a commercially available rapid-acting human insulin analogue administered subcutaneously (SC) within 15 minutes premeal or immediately after a meal to improve glycaemic control in diabetes patients. URLi is a novel insulin lispro formulation containing two locally acting excipients, treprostinil to induce local vasodilation and citrate to increase vascular permeability, thereby accelerating insulin lispro absorption
Jennifer Leohr, Eli Lilly and Company, Indianapolis, Indiana, USA, and colleagues aimed to compare the pharmacokinetics (PK), glucodynamics (GD), and tolerability following single and multiple daily subcutaneous doses of ultra-rapid lispro and Humalog in patients with type 2 diabetes mellitus (T2D).
The researchers conducted a two-part, randomized, double-blind Phase 1b study. Part A used a six-period crossover design to assess PK and GD response to a solid mixed meal tolerance test (MMTT) following a single dose of URLi or Humalog administered 15 minutes before, immediately before, or 15 minutes after the start of the meal. Part B evaluated URLi or Humalog during 2 weeks of multiple daily dosing with a parallel design.
The PK and GD were assessed following MMTTs at the beginning and end of the 2 weeks when insulins were administered immediately before the start of the meal.
The study revealed the following findings:
URLi increased the insulin exposure within the first 30 minutes postdose by 2.2-fold and reduced the time to the early half-maximal drug concentration by 22.6% compared with Humalog.
URLi resulted in better postprandial glucose lowering when dosed before, immediately before, or after a meal. In comparing the same meal-to-dose timing between the insulins, the postprandial glucose excursion over 5 hours was significantly reduced by 29%-105% for all three dose timings (−15, 0 and +15 minutes) with URLi.
The PK and GD were sustained after daily subcutaneous dosing for 2 weeks in patients with T2D.
URLi had more hypoglycaemic events during the MMTTs; few events occurred for both treatments during the 2 weeks of outpatient dosing.
The researchers concluded, "URLi demonstrated accelerated insulin lispro absorption and greater postprandial glucose reduction at different meal-to-dose timings compared with Humalog and was well tolerated in patients with T2D."
Reference:
The study titled, "Ultra rapid lispro (URLi) shows faster pharmacokinetics and reduces postprandial glucose excursions versus Humalog® in patients with type 2 diabetes mellitus in a randomized, controlled crossover meal test early-phase study," is published in the journal Diabetes, Obesity and Metabolism.
DOI: https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14561