Insulin Degludec: Four Times Lower Pharmacodynamic Variability Than Insulin Glargine Under Steady-state Conditions in Type 1 Diabetes

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 (AUC(GIR,0-24h,SS), CV 20% vs. 82%) and for the last 22 h [AUC(GIR,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 (GIR(max,SS), CV 18% vs. 60%). The lower within-subject variability of IDeg was consistent over time (CVs of 33% for AUC(GIR,0-2h,SS), 32% for AUC(GIR,10-12h,SS) and 33% for AUC(GIR,22-24h,SS)), whereas the variability of IGlar was higher and increased substantially 8 h post-dosing (CVs of 60% for AUC(GIR,0-2h,SS), 135% for AUC(GIR,10-12h,SS) and 115% for AUC(GIR,22-24h,SS)).

Conclusions: These results show that IDeg has a significantly more predictable glucose-lowering effect from day to day than IGlar.