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Diabetes Metab. 2018 Nov 26. pii: S1262-3636(18)30219-2. doi: 10.1016/j.diabet.2018.11.004. [Epub ahead of print]

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.

Author information

1
Diabetes Research Group, College of Medicine, Swansea University, Swansea SA2 8PP, UK. Electronic address: OwensDR@cardiff.ac.uk.
2
AMCR Institute Inc, Escondido, CA, USA.
3
University of Perugia, Perugia, Italy.
4
McGill University, Montreal, Quebec, Canada.

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.

KEYWORDS:

Basal insulins; Hypoglycaemia; Insulin degludec; Insulin glargine

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