title: A review of the pharmacological properties of insulin degludec and their clinical relevance.
abstract: Insulin degludec (IDeg) is a new-generation basal insulin with an ultra-long duration of action. To date, a large number of studies have been conducted to investigate the pharmacokinetic and pharmacodynamic properties of IDeg. Standardised methods for collection and analysis of blood samples (for pharmacokinetic endpoints) and euglycaemic clamp procedures (for pharmacodynamic endpoints) were applied across studies to enable cross-study evaluation of important pharmacokinetic and pharmacodynamic parameters. Data show that IDeg has a half-life of >25 h [compared with ~12 h for insulin glargine (IGlar)] and reaches steady state within 3 days of administration in all patient populations investigated. The pharmacokinetic profile of IDeg demonstrates an even distribution of exposure across one dosing interval. The pharmacodynamic profile of IDeg is flat and stable, demonstrated by an even distribution of glucose-lowering effect across all four 6-h intervals in a 24-h period (one dosing day). These properties were consistently demonstrated across different type 1 and type 2 diabetes mellitus patient populations, including those from different ethnic origins (both males and females with type 2 diabetes), the elderly, and patients with hepatic or renal impairment. IDeg has an ultra-long duration of action exceeding 42 h and demonstrates four times lower day-to-day within-subject variability in glucose-lowering effect than IGlar. This review discusses the pharmacokinetic and pharmacodynamic data accumulated thus far, and the relevance of these results from a clinical perspective.
authors.affiliation: Novo Nordisk A/S, Vandtårnsvej 108, 2860, Søborg, Denmark, hhaa@novonordisk.com.
authors.forename: Hanne
authors.initials: H
authors.lastname: Haahr
authors.forename: Tim
authors.initials: T
authors.lastname: Heise
mesh_terms: D002626:Chemistry, Pharmaceutical; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D049528:Insulin, Long-Acting / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; C571886:insulin degludec