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

• Published in: Diabetes & metabolism 2019-09, Vol.45 (4), p.330-340
• Main Authors: Owens, D.R., S Bailey, T., Fanelli, C.G., Yale, J.-F., Bolli, G.B.
• Format: Article
• Language: English
• Subjects: Basal insulins; Blood Glucose - drug effects; Blood Glucose - metabolism; Diabetes Mellitus, Type 1 - diagnosis; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - epidemiology; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - metabolism; Dose-Response Relationship, Drug; Humans; Hypoglycaemia; Hypoglycemia - chemically induced; Hypoglycemia - epidemiology; Hypoglycemia - metabolism; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - pharmacokinetics; Insulin degludec; Insulin glargine; Insulin Glargine - administration & dosage; Insulin Glargine - adverse effects; Insulin Glargine - pharmacokinetics; Insulin, Long-Acting - administration & dosage; Insulin, Long-Acting - adverse effects; Insulin, Long-Acting - pharmacokinetics; Prognosis
• ISSN: 1262-3636; 1878-1780
• DOI: 10.1016/j.diabet.2018.11.004

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. Available pharmacokinetic/pharmacodynamic publications comparing insulin degludec and insulin glargine were reviewed. 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