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

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.

Long-Term Efficacy and Safety of Ultra Rapid Lispro (URLi) in Adults with Type 1 Diabetes: The PRONTO-T1D Extension

“…A similar lowering of postprandial hypoglycemia was also observed at the week 26 primary endpoint [ 5 ]. These findings likely reflect the lower late insulin exposure and shorter duration of insulin exposure with URLi in comparison with lispro and other rapid insulin analogues as demonstrated in clinical pharmacology studies [ 1 , 11 ].…”

Improved postprandial glucose control with ultra rapid lispro versus lispro with continuous subcutaneous insulin infusion in type 1 diabetes: PRONTO‐Pump‐2

“…Lower rates of postmeal hypoglycaemia and decreased time below range were also observed with URLi in the PRONTO-T1D study and PRONTO-T1D CGM substudy. 8,14 These lower rates of hypoglycaemia are reflective of the shorter duration of action observed with URLi in clinical pharmacology studies, 15,16 which allows for improved PPG control without causing late postmeal hypoglycaemia.…”

Hundert Jahre – Insulin bleibt aktuell und notwendig

“…Mit dem ultraschnell wirkenden Insulin aspart kann jedoch wie beim Typ-1-Diabetes auch bei Menschen mit Typ-2-Diabetes eine noch bessere postprandiale Glukoseregulation erzielt werden [99]. Auch das ultraschnelle Insulin lispro (URLI) zeigte in Phase-I-Studien bei Typ-1-Diabetes [100] und Typ-2-Diabetes [101] vergleichbare pharmakodynamische Wirkungen.…”