Insulin degludec: four times lower pharmacodynamic variability than insulin glargine under steady-state conditions in type 1 diabetes

被引:323
作者
Heise, T. [1 ]
Hermanski, L. [1 ]
Nosek, L. [1 ]
Feldman, A. [1 ]
Rasmussen, S. [2 ]
Haahr, H. [3 ]
机构
[1] Profil Inst Stoffwechselforsch GmbH, D-41460 Neuss, Germany
[2] Novo Nordisk AS, Biostat, Soborg, Denmark
[3] Novo Nordisk AS, Insulin Clin Pharmacol, Soborg, Denmark
关键词
insulin degludec; insulin glargine; pharmacodynamics; pharmacokinetics; type; 1; diabetes; LONGACTING BASAL INSULIN; INJECTED INSULIN; BOLUS TREATMENT; NPH INSULIN; OPEN-LABEL; ABSORPTION; ANALOGS; PHASE-3; DETEMIR; ASPART;
D O I
10.1111/j.1463-1326.2012.01627.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims Insulin degludec (IDeg) is a new-generation basal insulin with an ultra-long duration of action. We compared the pharmacodynamic (PD) variability of IDeg and insulin glargine (IGlar) under steady-state conditions. Methods Day-to-day variability in glucose-lowering effect was investigated in 54 subjects with type 1 diabetes who underwent a 24-h euglycaemic glucose clamp on the 6th, 9th and 12th day of treatment with 0.4 U/kg of IDeg or IGlar once daily. Within-subject variability was estimated using a linear mixed model on log-transformed PD endpoints derived from the glucose infusion rate (GIR) profiles during the clamps. Results For IDeg the day-to-day variability in glucose-lowering effect was four-times lower than for IGlar for total metabolic effect (AUCGIR,0-24h,SS, CV 20% vs. 82%) and for the last 22 h [AUCGIR,2-24h,SS (not influenced by intravenous insulin during the clamp), CV 22% vs. 92%]. Furthermore, lower variability in the maximum effect was observed for IDeg vs. IGlar (GIRmax,SS, CV 18% vs. 60%). The lower within-subject variability of IDeg was consistent over time (CVs of 33% for AUCGIR,0-2h,SS, 32% for AUCGIR,10-12h,SS and 33% for AUCGIR,22-24h,SS), whereas the variability of IGlar was higher and increased substantially 8 h post-dosing (CVs of 60% for AUCGIR,0-2h,SS, 135% for AUCGIR,10-12h,SS and 115% for AUCGIR,22-24h,SS). Conclusions These results show that IDeg has a significantly more predictable glucose-lowering effect from day to day than IGlar.
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页码:859 / 864
页数:6
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