Low within‐ and between‐day variability in exposure to new insulin glargine 300 U/ml. Issue 3 (7th January 2015)

• Record Type: Journal Article
• Authors: Becker, R. H. A.; Nowotny, I.; Teichert, L.; Bergmann, K.; Kapitza, C.
• Is Part Of: Diabetes, obesity & metabolism. Volume 17:Issue 3(2015:Mar.)
• Page Start: 261
• Page End: 267
• Publication Date: 2015-01-07
• Subjects: Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.12416
• Languages: English
• ISSNs: 1462-8902

Abstract

<abstract abstract-type="main" id="dom12416-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="dom12416-sec-0001" sec-type="section"> <title>Aims</title> <p id="dom12416-para-0001">To 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).</p> </sec> <sec id="dom12416-sec-0002" sec-type="section"> <title>Methods</title> <p id="dom12416-para-0002">A 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.</p> </sec> <sec id="dom12416-sec-0003" sec-type="section"> <title>Results</title> <p id="dom12416-para-0003">The 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.</p> </sec> <sec id="dom12416-sec-0004" sec-type="section"> <title>Conclusions</title> <p id="dom12416-para-0004">Gla‐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.</p> </sec> </abstract>