Pharmacokinetics and Glucodynamics of Ultra Rapid Lispro (URLi) versus Humalog® (Lispro) in Patients with Type 2 Diabetes Mellitus: A Phase I Randomised, Crossover Study

Jennifer Leohr, Mary Anne Dellva, David E Coutant, Elizabeth LaBell, Tim Heise, Grit Andersen, Eric Zijlstra, Lidia Hermanski, Leszek Nosek, Helle Linnebjerg, Jennifer Leohr, Mary Anne Dellva, David E Coutant, Elizabeth LaBell, Tim Heise, Grit Andersen, Eric Zijlstra, Lidia Hermanski, Leszek Nosek, Helle Linnebjerg

Abstract

Background and objective: Ultra rapid lispro (URLi) is a novel insulin lispro formulation developed to more closely match physiological insulin secretion and improve postprandial glucose control. This study compared the insulin lispro pharmacokinetics and glucodynamics, safety and tolerability of URLi and Humalog® after a single subcutaneous dose in patients with type 2 diabetes mellitus (T2DM).

Methods: This was a phase I, randomised, two-period, two-treatment, double-blind, crossover study in 38 patients with T2DM. At each dosing visit, patients received either 15 units of URLi or Humalog, followed by a 10 h automated euglycaemic clamp procedure. Serum insulin lispro and blood glucose were measured.

Results: Insulin lispro appeared in the serum 5 min faster (p < 0.0001) and exposure was 6.4-fold greater in the first 15 min (p < 0.0001) with URLi versus Humalog. Exposure beyond 3 h postdose was 26% lower and the duration of exposure was 51 min shorter with URLi versus Humalog. Onset of insulin action was 13 min faster (p < 0.0001) and insulin action was 4.2-fold greater within the first 30 min (p < 0.0001) with URLi versus Humalog. Insulin action beyond 4 h postdose was 20% lower (p = 0.0099) with URLi versus Humalog. Overall insulin lispro exposure and total glucose infused were similar for URLi and Humalog. Both treatments were well tolerated.

Conclusions: This is the first study to investigate URLi in patients with T2DM using a euglycaemic clamp procedure. URLi demonstrated ultra-rapid pharmacokinetics and glucodynamics in patients with T2DM. CLINICALTRIALS.

Gov identifier: NCT03305822.

Conflict of interest statement

Jennifer Leohr, Mary Anne Dellva, David E. Coutant, Elizabeth LaBell and Helle Linnebjerg are employees and shareholders of Eli Lilly and Company. Tim Heise has received consulting fees or honoraria from Mylan and Novo Nordisk. Additionally, research funds to Tim Heise’s institution were received from Adocia, Boehringer Ingelheim, Dance Pharmaceuticals, Eli Lilly and Company, Gan & Lee Pharmaceuticals, Johnson & Johnson, Mars, Medimmune, Mylan, Nordic Bioscience, Novo Nordisk, Pfizer, Poxel, Saniona, Sanofi, Wockhardt and Zealand Pharma. Time Heise, Grit Andersen, Eric Zijlstra, Lidia Hermanski and Leszek Nosek are employees of Profil. Additionally, Eric Ziljstra has received payments for lectures from Eli Lilly and Company, Novo Nordisk, Roche Diabetes Care and Aerami Therapeutics.

Figures

Fig. 1
Fig. 1
Trial design. SC subcutaneous, U units, URLi ultra rapid lispro
Fig. 2
Fig. 2
Mean (± standard error [SE]) serum insulin lispro concentration–time profile for ultra rapid lispro (URLi) and Humalog. a Insulin lispro concentration–time profile 0–10 h after injection and b insulin lispro concentration–time profile 0–1 h after injection. The dashed line indicates the lower limit of quantification (LLOQ). U units
Fig. 3
Fig. 3
Mean locally weighted scatterplot smoothing (LOESS) fit of the glucose infusion rate over time for ultra rapid lispro (URLi) and Humalog. a Glucose infusion rate profile 0–10 h after injection and b glucose infusion rate profile 0–2 h after injection. U units
Fig. 4
Fig. 4
Mean (± standard error [SE]) C-peptide profiles following a single 15-unit (U) subcutaneous injection of ultra rapid lispro (URLi) or Humalog

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Source: PubMed

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