title: Safety and efficacy of inhaled human insulin (Exubera) during discontinuation and readministration of therapy in adults with type 1 diabetes: A 3-year randomized controlled trial.
abstract: OBJECTIVE
  To assess pulmonary safety during discontinuation and readministration of inhaled human insulin (EXU; Exubera((R)) insulin human [rDNA origin]) Inhalation Powder) therapy in adults with type 1 diabetes.
  
  
  METHODS
  Patients were randomized to receive basal insulin plus either pre-meal EXU (n=290) or a short-acting subcutaneous (SC) insulin (n=290) for 2 years (comparative phase), followed by 6 months of SC insulin (washout) and 6 months of their original therapy (readministration). Highly standardized lung function tests were performed throughout.
  
  
  RESULTS
  Small treatment group differences favoring SC insulin in change from baseline forced expiratory volume in 1s (FEV(1)) and carbon monoxide diffusing capacity (DL(CO)) occurred early and were non-progressive. These differences resolved during washout and recurred at the same magnitude during readministration. Both groups maintained glycemic control, and hypoglycemic event rates were similar. In the EXU group, insulin antibody (IAb) levels plateaued at 12 months, declined to near baseline levels during washout and increased during readministration to levels observed in the comparative phase.
  
  
  CONCLUSIONS
  FEV(1) and DL(CO) changes observed during discontinuation and readministration of EXU therapy are consistent with a reversible, non-progressive and non-pathological effect on lung function. EXU readministration is not associated with an augmented IAb response.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, University of Miami, 1450 NW 10th Avenue, Suite 3054, Miami, FL 33136, United States. jskyler@miami.edu
authors.forename: Jay S
authors.initials: JS
authors.lastname: Skyler
authors.forename: Priscilla A
authors.initials: PA
authors.lastname: Hollander
authors.forename: Lois
authors.initials: L
authors.lastname: Jovanovic
authors.forename: Sol
authors.initials: S
authors.lastname: Klioze
authors.forename: Alan
authors.initials: A
authors.lastname: Krasner
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Riese
authors.forename: Joann
authors.initials: J
authors.lastname: Reis
authors.forename: Pamela
authors.initials: P
authors.lastname: Schwartz
authors.forename: William
authors.initials: W
authors.lastname: Duggan
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: C473734:Exubera; D007004:Hypoglycemic Agents; D007328:Insulin