Low within‐ and between‐day variability in exposure to new insulin glargine 300 U/ml

Abstract

AimsTo characterize the variability in exposure and metabolic effect of insulin glargine 300 U/ml (Gla-300) at steady state in people with type 1 diabetes (T1DM).MethodsA total of 50 participants with T1DM underwent two 24-h euglycaemic clamps in steady-state conditions after six once-daily administrations of 0.4 U/kg Gla-300 in a double-blind, randomized, two-treatment, two-period, crossover clamp study. Participants were randomized to receive Gla-300 as a standard cartridge formulation in the first treatment period, and as a formulation with enhanced stability through polysorbate-20 addition in the second treatment period, or vice versa. This design allowed the assessment of bioequivalence between formulations and, subsequently, within- and between-day variability.ResultsThe cumulative exposure and effect of Gla-300 developed linearly over 24 h, and were evenly distributed across 6- and 12-h intervals. Diurnal fluctuation in exposure (within-day variability) was low; the peak-to-trough ratio of insulin concentration profiles was <2, and both the swing and peak-to-trough fluctuation were <1. Day-to-day reproducibility of exposure was high: the between-day within-subject coefficients of variation for total systemic exposure (area under the serum insulin glargine concentration time curve from time 0 to 24 h after dosing) and maximum insulin concentration were 17.4% [95% confidence interval (CI) 15–21] and 33.4% (95% CI 28–41), respectively. Reproducibility of the metabolic effect was lower than that of exposure.ConclusionsGla-300 provides predictable, evenly distributed 24-h coverage as a result of low fluctuation and high reproducibility in insulin exposure, and appears suitable for effective basal insulin use.

New Long-Acting Basal Insulins: Does Benefit Outweigh Cost?

“…2), resulting in a retarded and prolonged dissolution from the subcutaneous tissue compared with generally available standard glargine (U100) ( Tables 1 and 2). Also, its metabolic degradation to the metabolites M1 (GlyA21 insulin) and M2 (GlyA21, des-ThrB30) is similar to that of insulin glargine U100 (42). These metabolites show binding characteristics to the insulin receptor and IGF-1 receptor comparable with human insulin.…”

“…The findings from the DEVOTE study in 7,500 high-risk individuals with type 2 diabetes will be invaluable owing to its prospective, double-blind design. Glargine U300 is a new higherstrength formulation of insulin glargine at 300 IU/mL rather than the usual glargine at 100 IU/mL, which alters its pharmacokinetic and pharmacodynamic properties (1,3,4,22,25,26,41,42). Glargine U300 forms a more compact subcutaneous depot with its surface area reduced by half and its volume by two-thirds (Fig.…”

Insulin U100, 200, 300 or 500?

“…19,20 Within-subject variability was lower with IGlarU300 than previously reported with IGlarU100. 21,22 Data from phase III clinical trials (EDITION) have shown that IGlarU300 results in a distinct pharmacokinetic and pharmacodynamic profile. It also has a longer duration of action and variability is much less than for IGlarU100.…”

Achieve control: a pragmatic clinical trial of insulin glargine 300 U/mL versus other basal insulins in insulin-naïve patients with type 2 diabetes

“…In pharmacokinetics and pharmacodynamics studies, insulin glargine 300 U/mL (Gla-300) has demonstrated low variability in exposure over 24 h, a more consistent activity profile, and prolonged maintenance of glucose control compared with insulin glargine 100 U/mL (Gla-100) [8][9][10]. In the randomized, controlled Phase III EDITION clinical trial program, Gla-300 was shown to be non-inferior to Gla-100 in reducing HbA1c levels, without increasing the risk of hypoglycemia versus Gla-100 in patients with type 1 diabetes (T1D) or T2D at 6 months [11][12][13][14] and at 1 year [15,16].…”