title: Efficacy and safety of AIR inhaled insulin compared to insulin lispro in patients with type 1 diabetes mellitus in a 6-month, randomized, noninferiority trial.
abstract: BACKGROUND
  Patients with type 1 diabetes may prefer features of AIR inhaled insulin (developed by Alkermes, Inc. [Cambridge, MA] and Eli Lilly and Company [Indianapolis, IN]; AIR is a registered trademark of Alkermes, Inc.) over insulin injection, but the two methods need to be compared for efficacy and safety.
  
  
  METHODS
  This multicenter, 6-month, parallel-group, noninferiority trial had 500 patients with type 1 diabetes randomized to morning doses of basal insulin glargine plus either preprandial injectable insulin lispro or preprandial AIR insulin. We hypothesized that AIR insulin is noninferior (upper bound of the 95% confidence interval < or = 0.4%) to insulin lispro for change-from-baseline hemoglobin A1C (A1C).
  
  
  RESULTS
  Baseline A1C was 7.95 +/- 0.08% for both groups. At end point, A1C was lower with insulin lispro than with AIR insulin by 0.27% (95% confidence interval 0.11, 0.43; P< 0.001). Noninferiority of AIR insulin to insulin lispro was not demonstrated, but similar percentages of patients in each group achieved A1C <7.0% (P = 0.448). Overall daily blood glucose was similar between groups at baseline (P = 0.879) and end point (P = 0.161). Two-hour postprandial blood glucose change from baseline was significantly (P < 0.001) higher with AIR insulin (20.77 +/- 4.33 mg/dL at 3 months and 15.85 +/- 3.08 mg/dL at end point) than with insulin lispro (3.29 +/- 4.14 mg/dL at 3 months and 1.67 +/- 2.91 mg/dL at end point). Overall hypoglycemia was similar between treatment groups (P = 0.355). The AIR insulin group had greater decrease in diffusing capacity of the lung for carbon monoxide at end point (P = 0.020) and greater incidence of cough (P = 0.024) and dyspnea (P = 0.030). Body weight decreased in the AIR insulin group and increased in the insulin lispro group.
  
  
  CONCLUSIONS
  Insulin lispro provided lower A1C than AIR insulin, but the difference may not be clinically relevant.
authors.affiliation: Instituto de Endocrinología, Diabetes & Metabolismo, Toa Baja, Puerto Rico.
authors.forename: Angel L
authors.initials: AL
authors.lastname: Comulada
authors.forename: Eric
authors.initials: E
authors.lastname: Renard
authors.forename: Masako
authors.initials: M
authors.lastname: Nakano
authors.forename: Nadeem
authors.initials: N
authors.lastname: Rais
authors.forename: Xuejing
authors.initials: X
authors.lastname: Mao
authors.forename: David M
authors.initials: DM
authors.lastname: Webb
authors.forename: Zvonko
authors.initials: Z
authors.lastname: Milicevic
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D015992:Body Mass Index; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007330:Insulin Antibodies / Q000097:blood; D000069036:Insulin Glargine; D061268:Insulin Lispro; D049528:Insulin, Long-Acting; D008297:Male; D008875:Middle Aged; D012449:Safety; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D007330:Insulin Antibodies; D000069036:Insulin Glargine; D061268:Insulin Lispro; D049528:Insulin, Long-Acting