title: The Distinct Prandial and Basal Pharmacodynamics of IDegAsp Observed in Younger Adults Are Preserved in Elderly Subjects with Type 1 Diabetes.
abstract: BACKGROUND
  Management of diabetes in elderly patients is complicated by the elevated risk of insulin-induced hypoglycaemia. This is the first study to report the pharmacodynamic and pharmacokinetic characteristics of IDegAsp (insulin degludec [IDeg]/insulin aspart [IAsp]), a soluble co-formulation of a long-acting basal insulin analogue (IDeg) and a rapid-acting insulin analogue (IAsp) in a single injection, in elderly and younger adult subjects with type 1 diabetes using a glucose clamp.
  
  
  METHODS
  In this randomised, single-centre, double-blind, single-dose (SD), two-period, crossover trial, 15 elderly subjects (aged ≥ 65 years) and 13 younger adults (aged 18-35 years) with type 1 diabetes were randomly assigned to two SD administrations of 0.5 U/kg IDegAsp or biphasic insulin aspart 30 (control) followed by a 26-h euglycaemic glucose clamp and 120-h pharmacokinetic blood sampling. The glucose infusion rate (GIR) profiles were extrapolated to simulated steady-state (SS) conditions using pharmacodynamic models.
  
  
  RESULTS
  IDegAsp GIR profiles showed a distinct peak and rapid onset of action from IAsp followed by a separate and flat basal action from IDeg. Mean 24-h area under the GIR curve was similar in elderly subjects vs. younger adults (mean ratio 1.01 [95% confidence interval 0.69-1.47]). Simulated SS pharmacodynamic profiles with once-daily IDegAsp showed a parallel upshift in GIR profiles vs. SD profiles. The shape of the IDegAsp pharmacodynamic profile was retained with twice-daily dosing under simulated SS conditions. IDegAsp was well tolerated.
  
  
  CONCLUSIONS
  The distinct prandial and basal pharmacodynamics of IDegAsp observed in younger adults were preserved in elderly subjects with type 1 diabetes. The glucose-lowering effect of IDegAsp was similar in elderly subjects and younger adults with type 1 diabetes.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria, martina.brunner@medunigraz.at.
authors.forename: Martina
authors.initials: M
authors.lastname: Brunner
authors.forename: Thomas
authors.initials: T
authors.lastname: Pieber
authors.forename: Stefan
authors.initials: S
authors.lastname: Korsatko
authors.forename: Harald
authors.initials: H
authors.lastname: Kojzar
authors.forename: Anne Louise
authors.initials: AL
authors.lastname: Svendsen
authors.forename: Hanne
authors.initials: H
authors.lastname: Haahr
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D019468:Disease Management; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000627:therapeutic use; D049528:Insulin, Long-Acting / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; C578220:insulin degludec, insulin aspart drug combination