BACKGROUND AND OBJECTIVE: Insulin degludec (IDeg) is a new-generation basal insulin that forms soluble multi-hexamers upon subcutaneous injection, resulting in a depot from which IDeg monomers are slowly and continuously absorbed to provide an ultra-long action profile. This double-blind, crossover, randomized study compared the pharmacokinetic and pharmacodynamic properties between IDeg 100 U/mL (U100) and IDeg 200 U/mL (U200) under steady-state (SS) conditions in subjects with type 1 diabetes mellitus. METHODS:Participants (n = 33 adults) underwent 8-day treatment periods with 0.4 U/kg IDeg U100 and IDeg U200 given once daily with insulin aspart at mealtimes. On day 8, a 26-h euglycaemic glucose clamp (5.5 mmol/L) was performed. RESULTS: The concentration-time profiles of IDeg U100 and IDeg U200 were similar, and a post-hoc analysis showed bioequivalence between these formulations, as the 90 % confidence intervals (CIs) of the U200/U100 ratios for area under the steady-state serum IDeg concentration-time curve during a dosing interval (τ; 0-24 h) (AUCτ,SS,IDeg) (0.99 [0.91-1.07]) and maximum steady-state IDeg concentration during a dosing interval (τ) (C max,SS,IDeg) (0.93 [0.84-1.02]) were within the interval 0.80-1.25. Comparable glucose infusion rates (GIR) were observed for IDeg U100 and IDeg U200 (AUCτ,SS,GIR [mg/kg]: 2,255 vs. 2,123) and the mean ratio (95 % CI) of IDeg U200/U100 for the primary endpoint (AUCτ,SS,GIR) was 0.94 [0.86-1.03]. For both formulations, the glucose-lowering effect of IDeg was evenly distributed between the first and second 12 h post-dosing (U100: AUC12,SS,GIR/AUC24,SS,GIR = 48 %; U200: AUC12,SS,GIR/AUC24,SS,GIR = 46 %). Both formulations were well tolerated, and no safety events of significance were identified. CONCLUSION: IDeg U100 and U200 formulations are bioequivalent and have similar pharmacodynamic profiles at SS, implying that they can be used interchangeably in clinical practice.
RCT Entities:
BACKGROUND AND OBJECTIVE:Insulin degludec (IDeg) is a new-generation basal insulin that forms soluble multi-hexamers upon subcutaneous injection, resulting in a depot from which IDeg monomers are slowly and continuously absorbed to provide an ultra-long action profile. This double-blind, crossover, randomized study compared the pharmacokinetic and pharmacodynamic properties between IDeg 100 U/mL (U100) and IDeg 200 U/mL (U200) under steady-state (SS) conditions in subjects with type 1 diabetes mellitus. METHODS:Participants (n = 33 adults) underwent 8-day treatment periods with 0.4 U/kg IDeg U100 and IDeg U200 given once daily with insulin aspart at mealtimes. On day 8, a 26-h euglycaemic glucose clamp (5.5 mmol/L) was performed. RESULTS: The concentration-time profiles of IDeg U100 and IDeg U200 were similar, and a post-hoc analysis showed bioequivalence between these formulations, as the 90 % confidence intervals (CIs) of the U200/U100 ratios for area under the steady-state serum IDeg concentration-time curve during a dosing interval (τ; 0-24 h) (AUCτ,SS,IDeg) (0.99 [0.91-1.07]) and maximum steady-state IDeg concentration during a dosing interval (τ) (C max,SS,IDeg) (0.93 [0.84-1.02]) were within the interval 0.80-1.25. Comparable glucose infusion rates (GIR) were observed for IDeg U100 and IDeg U200 (AUCτ,SS,GIR [mg/kg]: 2,255 vs. 2,123) and the mean ratio (95 % CI) of IDeg U200/U100 for the primary endpoint (AUCτ,SS,GIR) was 0.94 [0.86-1.03]. For both formulations, the glucose-lowering effect of IDeg was evenly distributed between the first and second 12 h post-dosing (U100: AUC12,SS,GIR/AUC24,SS,GIR = 48 %; U200: AUC12,SS,GIR/AUC24,SS,GIR = 46 %). Both formulations were well tolerated, and no safety events of significance were identified. CONCLUSION:IDeg U100 and U200 formulations are bioequivalent and have similar pharmacodynamic profiles at SS, implying that they can be used interchangeably in clinical practice.
Authors: R E Ratner; S C L Gough; C Mathieu; S Del Prato; B Bode; H Mersebach; L Endahl; B Zinman Journal: Diabetes Obes Metab Date: 2012-12-03 Impact factor: 6.577
Authors: Laura M Nally; Jennifer L Sherr; Michelle A Van Name; Anisha D Patel; William V Tamborlane Journal: Expert Rev Clin Pharmacol Date: 2019-05 Impact factor: 5.045
Authors: Andrea C Tricco; Huda M Ashoor; Jesmin Antony; Zachary Bouck; Myanca Rodrigues; Ba' Pham; Paul A Khan; Vera Nincic; Nazia Darvesh; Fatemeh Yazdi; Marco Ghassemi; John D Ivory; Areti Angeliki Veroniki; Catherine H Yu; Lorenzo Moja; Sharon E Straus Journal: J Gen Intern Med Date: 2021-03-19 Impact factor: 6.473