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

Abstract

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. 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. 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}). These results show that IDeg has a significantly more predictable glucose‐lowering effect from day to day than IGlar.