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

Author(s): Heise T ; Hermanski L ; Nosek L ; Feldman A ; Rasmussen S ; Haahr H

Corporate source(s)

Heise T, Profil Inst Stoffwechselforsch GmbH, D-41460 Neuss, Germany, tim.heise@profil.com

Source

Diabetes Obesity and Metabolism 2012, Vol. 14, pg. 859-864

Abstract

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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