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Ultra‐long‐acting insulin degludec has a flat and stable glucose‐lowering effect in type 2 diabetes
Author(s) -
Heise T.,
Nosek L.,
Bøttcher S. G.,
Hastrup H.,
Haahr H.
Publication year - 2012
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/j.1463-1326.2012.01638.x
Subject(s) - insulin degludec , pharmacokinetics , dosing , medicine , diabetes mellitus , insulin , endocrinology , pharmacodynamics , concomitant , clamp , type 2 diabetes , basal (medicine) , area under the curve , glucose clamp technique , basal insulin , pancreatic hormone , insulin resistance , mechanical engineering , clamping , engineering
Aims Insulin degludec ( IDeg ) is a new‐generation, ultra‐long‐acting basal insulin that forms soluble multihexamers upon subcutaneous injection, resulting in a depot from which IDeg is absorbed slowly and continuously into circulation. This double‐blind, two‐period, incomplete block cross‐over trial investigated the pharmacodynamic and pharmacokinetic properties of IDeg at steady state ( SS ) in people with type 2 diabetes. Methods Forty‐nine subjects treated with insulin without concomitant oral anti‐diabetic drugs were given IDeg (0.4, 0.6 and/or 0.8 U/kg) once daily for two 6‐day periods, separated by an interval of 13–21 days. Following dosing on Day 6, subjects underwent a 26‐h euglycaemic glucose clamp (Biostator®; clamp blood glucose level: 90 mg/dl; 5.0 mmol/l). Pharmacokinetic samples were taken until 120 h after last dosing. Results For all dose levels, the mean glucose infusion rate ( GIR ) profiles were flat and stable. The glucose‐lowering effect of IDeg was evenly distributed over the dosing interval τ, with area under the curve ( AUC ) for each of the four 6‐h intervals being approximately 25% of the total AUC ( AUC GIR ,τ, SS ). Total glucose‐lowering effect increased linearly with increasing dose. The blood glucose levels of all subjects stayed very close to the clamp target until end of clamp. The terminal half‐life of IDeg was approximately 25 h at steady state. IDeg was well tolerated and no safety concerns were identified. No injection site reactions were reported. Conclusions IDeg has a flat and consistent glucose‐lowering effect in people with type 2 diabetes.