title: Assessment of long-term immunological and pulmonary safety of inhaled human insulin with up to 24 months of continuous therapy.
abstract: BACKGROUND
  This study was performed to characterize the long-term safety and efficacy of inhaled human insulin (EXU; Exubera * (insulin human [rDNA origin]) Inhalation Powder). * Pfizer Inc, New York, NY, USA.
  
  
  METHODS
  Patients with type 1 or type 2 diabetes (N = 1290) who had successfully completed one of six controlled EXU open-label trials elected to receive open-label treatment with EXU for up to 3 years, after which they were randomized to discontinue EXU or to continue therapy for 6 months, then discontinue. Immunologic safety was assessed by insulin antibody (IAb) binding, and pulmonary safety was assessed by tests for forced expiratory volume in 1 second (FEV(1)) and carbon monoxide diffusing capacity (DL(CO)). In addition, changes over time in IAbs were compared with changes in FEV(1), DL(CO), hypoglycemia, and efficacy.
  
  
  RESULTS
  Antibody binding increased in patients with either type 1 or type 2 diabetes after initiation of EXU and plateaued within 6-12 months (increases were higher in patients with type 1 diabetes than in patients with type 2 diabetes). Decreases in FEV(1) occurred primarily during the first 3-6 months of EXU therapy. Among adult patients in the All Subjects set, the mean (± SE) annualized rate of decline in FEV(1) was -0.053 ± 0.007 liters/year (95% CI, -0.065, -0.040) in adult patients with type 1 diabetes, and -0.076 ± 0.005 liters/year (95% CI, -0.085, -0.067) in patients with type 2 diabetes. Changes in DL(CO) occurred primarily during the first 3-6 months of EXU therapy. Among adult patients, in the All Subjects set, the mean (± SE) annual decline in DL(CO) was -0.738 ± 0.097 mL/min/mmHg/year (95% CI, -0.927, -0.548) and -0.688 ± 0.082 mL/min/mmHg/year (95% CI, -0.849, -0.527) in patients with type 1 and type 2 diabetes, respectively. Antibody binding did not correlate with changes in glycemic control, lung function, dose, or hypoglycemia. Following discontinuation of EXU, IAbs decreased to near baseline levels.
  
  
  CONCLUSIONS
  These results are consistent with other trials showing long-term maintenance of safety and efficacy of EXU despite insulin antibody formation and small treatment group differences in pulmonary function. A limitation of the study was the lack of a comparator therapy.
authors.affiliation: Pennington Biomedical Research Center,Baton Rouge, LA 70808, USA. CefaluWT@pbrc.edu
authors.forename: William T
authors.initials: WT
authors.lastname: Cefalu
authors.forename: Nancy J V
authors.initials: NJ
authors.lastname: Bohannon
authors.forename: S
authors.initials: S
authors.lastname: Edwin Fineberg
authors.forename: John G
authors.initials: JG
authors.lastname: Teeter
authors.forename: Pamela F
authors.initials: PF
authors.lastname: Schwartz
authors.forename: Joann M
authors.initials: JM
authors.lastname: Reis
authors.forename: Alan S
authors.initials: AS
authors.lastname: Krasner
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D007107:Immune System / Q000187:drug effects* / Q000503:physiopathology; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C473734:Exubera; D007004:Hypoglycemic Agents; D007328:Insulin