title: Antibody response to inhaled insulin in patients with type 1 or type 2 diabetes. An analysis of initial phase II and III inhaled insulin (Exubera) trials and a two-year extension trial.
abstract: OBJECTIVE
  To compare antibody responses to inhaled human insulin vs. sc human insulin and to determine whether insulin antibody binding is associated with adverse clinical consequences.
  
  
  METHODS
  Insulin antibody data from initial phase II/III trials were analyzed comparing the efficacy and safety of inhaled insulin with various agents, including sc insulin. Additionally, data from a 24-month extension of the phase III studies were examined. Data were pooled into the following three groups based on insulin treatment status at baseline: patients with type 1 diabetes, and patients with type 2 diabetes using insulin and not using insulin at baseline. Ig class analysis was also performed on randomly selected sera from type 1 patients at the end of the initial trials.
  
  
  RESULTS
  In the initial trials, greater insulin antibody binding was observed in patients receiving inhaled insulin vs. sc insulin. The greatest antibody responses to inhaled insulin were observed in patients with type 1 diabetes [nonparametric comparison of medians at the end of the study, 22.0% binding (unadjusted 95% confidence interval: 19.5, 24.5)], and the lowest responses were observed in non-insulin-using patients with type 2 diabetes in which there was no difference in median values at the end of the study. There were no correlations between antibody binding and glycemic control (measured using glycosylated hemoglobin), insulin dose requirements, hypoglycemic events, or pulmonary function (measured by changes in forced expiratory volume in 1 sec and diffusion capacity of carbon monoxide). Antibody responses were IgG in type. Differences in antibody levels observed in patients with type 1 vs. type 2 diabetes were maintained over the 24-month extension trials. Peak antibody levels across all groups were generally observed after 6-12 months of insulin therapy. Inhaled insulin therapy was not associated with a greater incidence of allergy or other hypersensitivity reactions.
  
  
  CONCLUSIONS
  Inhaled insulin was observed to produce a larger antibody response than sc insulin. Insulin antibody binding has not been associated with adverse clinical consequences in trials to date.
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. efineber@iupui.edu
authors.forename: S Edwin
authors.initials: SE
authors.lastname: Fineberg
authors.forename: Tom
authors.initials: T
authors.lastname: Kawabata
authors.forename: Deborah
authors.initials: D
authors.lastname: Finco-Kent
authors.forename: Cameron
authors.initials: C
authors.lastname: Liu
authors.forename: Alan
authors.initials: A
authors.lastname: Krasner
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000917:Antibody Formation; D001666:Binding Sites, Antibody; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000276:immunology; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D007330:Insulin Antibodies / Q000097:blood*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D007330:Insulin Antibodies