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Steady‐state pharmacokinetics and glucodynamics of the novel, long‐acting basal insulin LY2605541 dosed once‐daily in patients with type 2 diabetes mellitus
Author(s) -
Sinha V. P.,
Howey D. C.,
Choi S. L.,
Mace K. F.,
Heise T.
Publication year - 2014
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12222
Subject(s) - pharmacokinetics , insulin , medicine , endocrinology , basal (medicine) , type 2 diabetes mellitus , diabetes mellitus , hypoglycemia , area under the curve , type 1 diabetes , type 2 diabetes
Aims To assess the pharmacokinetics ( PK ) and glucodynamics ( GD ) of LY2605541 in patients with type 2 diabetes mellitus. Methods This parallel‐group, open‐label, dose‐escalation study examined the PK and GD of basal insulin LY2605541 after single and multiple‐dose administration. Fixed doses of LY2605541 (0.33–1.00 U/kg) were given once‐daily ( QD ) for 14 days to insulin‐treated patients with type 2 diabetes. A 24‐h euglycaemic glucose clamp was conducted on days 1 and 14. Results PK steady state was achieved within 7–10 days and the peak‐to‐trough fluctuation was <2, translating to a nearly ‘peakless’ glucose infusion rate at steady state and with a duration of action of at least 24 h. Across dose levels t 1/2 ranged from 44.7 to 75.5 h (˜2–3 days). As steady state was achieved, there were dose‐dependent reductions in the prandial insulin dose and in fasting blood glucose, which decreased to 60–100 mg/dl across dose levels. Within‐patient variability was <14 and <26% for the area under the concentration versus time curve ( AUC ) of the 8‐point blood glucose profile and fasting blood glucose, respectively. The nocturnal glucose control between 03:00 and 09:00 hours was relatively unchanged. Mild hypoglycaemia was the most common adverse event. Conclusions In this Phase I study of fixed LY2605541 doses without titration, LY2605541 was well‐tolerated and demonstrated a flat PK and GD profile accompanied by glucose normalization, prandial insulin dose reduction and no severe hypoglycaemia.