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. Issue 2 (27th October 2021)

• Record Type: Journal Article
• Authors: Leohr, Jennifer; Kazda, Christof; Liu, Rong; Reddy, Shobha; Dellva, Mary Anne; Matzopoulos, Mark; Loh, Mei Teng; Hardy, Thomas; Klein, Oliver; Kapitza, Christoph
• Is Part Of: Diabetes, obesity & metabolism. Volume 24:Issue 2(2022)
• Page Start: 187
• Page End: 195
• Publication Date: 2021-10-27
• Subjects: insulin therapy -- pharmacodynamics -- pharmacokinetics -- type 2 diabetes mellitus -- ultra‐rapid insulin; Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.14561
• Languages: English
• ISSNs: 1462-8902

Abstract

Abstract: Aims: To compare the pharmacokinetics (PK), glucodynamics (GD) and tolerability following single and multiple daily subcutaneous doses of ultra rapid lispro (URLi) and Humalog® in patients with type 2 diabetes mellitus (T2D). Materials and Methods: This was 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. Results: 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. Overall, 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. Conclusions: 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.