Journal Article

Lower Within-Subject Variability of Insulin Detemir in Comparison to NPH Insulin and Insulin Glargine in People With Type 1 Diabetes

Leszek Nosek, Eberhard Draeger, Christoph Kapitza, Birgitte Biilmann Rønn, Lars Endahl, Lutz Heinemann, Tim Heise

2004

Overview

Lower Within-Subject Variability of Insulin Detemir in Comparison to NPH Insulin and Insulin Glargine in People With Type 1 Diabetes Tim Heise 1 , Leszek Nosek 1 , Birgitte Biilmann Rønn 2 , Lars Endahl 2 , Lutz Heinemann 1 , Christoph Kapitza 1 and Eberhard Draeger 2 1 Profil Institut für Stoffwechselforschung, Neuss, Germany 2 Novo Nordisk, Bagsvaerd, Denmark Address correspondence and reprint requests to Tim Heise, MD, Profil Institut für Stoffwechselforschung, Hellersbergstr. 9, D-41460 Neuss, Germany. E-mail: tim.heise{at}profil-research.de Abstract The aim of this randomized double-blind study was to compare the within-subject variability of the glucose-lowering effect of a novel insulin analog, insulin detemir, with that of insulin glargine and NPH insulin in people with type 1 diabetes. Fifty-four subjects (32 males and 22 females, age 38 ± 10 years [mean ± SD], BMI 24 ± 2 kg/m 2 , HbA 1c 7.5 ± 1.2%, diabetes duration 18 ± 9 years) participated in this parallel group comparison. Each subject received four single subcutaneous doses of 0.4 units/kg of either insulin detemir ( n = 18), insulin glargine ( n = 16), or human NPH insulin ( n = 17) under euglycemic glucose clamp conditions (target blood glucose concentration 5.5 mmol/l) on four identical study days. The pharmacodynamic (glucose infusion rates [GIRs]) and pharmacokinetic (serum concentrations of insulin detemir, human insulin, and insulin glargine) properties of the basal insulin preparations were recorded for 24 h postdosing. Insulin detemir was associated with significantly less within-subject variability than both NPH insulin and insulin glargine, as assessed by the coefficient of variation (CV) for the pharmacodynamic end points studied [GIR-AUC (0–12 h) 27% (detemir) vs. 59% (NPH) vs. 46% (glargine); GIR-AUC (0–24 h) 27 vs. 68 vs. 48%; GIR max 23 vs. 46 vs. 36%; P < 0.001 for all comparisons]. Insulin detemir also provided less within-subject variability in the pharmacokinetic end points: maximal concentration ( C max ) 18 vs. 24 vs. 34%; INS-AUC (0–∞) 14 vs. 28 vs. 33%. The results suggest that insulin detemir has a significantly more predictable glucose-lowering effect than both NPH insulin and insulin glargine. AUC, area under the curve ELISA, enzyme-linked immunosorbent assay GIR, glucose infusion rate GIRmax, maximum GIR Footnotes L.H. has been on advisory boards for, received honoraria and consulting fees from, and received research funding from Aventis, Pfizer, and Novo Nordisk. E.D. holds stocks in Aventis. Accepted March 3, 2004. Received November 1, 2003. DIABETES

• Publisher: American Diabetes Association
• Subject: Adult / Associated diseases and complications / Biological and medical sciences / Carrier Proteins - adverse effects / Carrier Proteins - blood / Carrier Proteins - therapeutic use / Dextrose / Diabetes / Diabetes mellitus / Diabetes Mellitus, Type 1 - blood / Diabetes Mellitus, Type 1 - drug therapy / Diabetes. Impaired glucose tolerance / Dose-Response Relationship, Drug / Double-Blind Method / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Etiopathogenesis. Screening. Investigations. Target tissue resistance / Female / Glucose / Glucose - administration & dosage / Health aspects / Humans / Hypoglycemic Agents - adverse effects / Hypoglycemic Agents - blood / Hypoglycemic Agents - therapeutic use / Insulin / Insulin - adverse effects / Insulin - analogs & derivatives / Insulin - blood / Insulin - therapeutic use / Insulin Detemir / Insulin Glargine / Insulin, Isophane - adverse effects / Insulin, Isophane - blood / Insulin, Isophane - therapeutic use / Insulin, Long-Acting / Male / Medical sciences / Middle Aged / Time Factors / Treatment Outcome