Clinical relevance of pharmacokinetic and pharmacodynamic profiles of insulin degludec (100, 200?U/mL) and insulin glargine (100, 300?U/mL)?–?a review of evidence and clinical interpretation - 15/08/19
Abstract |
Aim |
Second-generation basal insulin analogues (e.g. insulin degludec, insulin glargine 300 U/mL), were designed to further extend the duration of insulin action and reduce within-day and day-to-day variability, and consequently hypoglycaemia risk, versus earlier long-acting basal insulins. This review examines the pharmacokinetic/pharmacodynamic characteristics of insulin degludec (100, 200 U/mL) and insulin glargine (100, 300 U/mL), and their influence on clinical outcomes.
Methods |
Available pharmacokinetic/pharmacodynamic publications comparing insulin degludec and insulin glargine were reviewed.
Results |
Both insulin degludec and insulin glargine 300 U/mL have more prolonged and stable pharmacokinetic/pharmacodynamic profiles than the earlier basal insulin analogue, insulin glargine 100 U/mL. Insulin glargine 300 U/mL (0.4 U/kg, morning) showed a more stable pharmacodynamic profile (20% lower within-day variability [P = 0.047]) and more even 24-h distribution (over each 6-h quartile) than insulin degludec 100 U/mL, whereas the supratherapeutic 0.6 U/kg dose demonstrated a similar, albeit non-significant, trend. In contrast, a second clamp study indicated lower day-to-day variability in the 24-h glucose-lowering effect (variance ratio 3.70, P < 0.0001), and more even dosing over each 6-h quartile, with insulin degludec 200 U/mL versus insulin glargine 300 U/mL (0.4 U/kg, evening). Methodological differences and differences in bioequivalence that may explain these discrepancies are discussed.
Conclusions |
Compared with earlier insulin analogues, second-generation basal insulins have improved pharmacokinetic/pharmacodynamic profiles that translate into clinical benefits, primarily reduced nocturnal-hypoglycaemia risk. Additional head-to-head comparisons of insulin degludec and insulin glargine 300 U/mL at bioequivalent doses, utilising continuous glucose monitoring and/or real-world evidence, are required to elucidate the differences in their pharmacological and clinical profiles.
Le texte complet de cet article est disponible en PDF.Keywords : Basal insulins, Insulin degludec, Insulin glargine, Hypoglycaemia
Abbreviations : AUCGIR,τ,SS, CGM, GIR, GIR-AUC, Gla-100, Gla-300, IDeg, INS, INS-C, NPH, PD, PK, PTF, T1DM, T2DM
Plan
Vol 45 - N° 4
P. 330-340 - septembre 2019 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.