Two-year pulmonary safety and efficacy of inhaled human insulin (Exubera) in adult patients with type 2 diabetes.
OBJECTIVE
The purpose of this study was to evaluate the 2-year pulmonary safety of inhaled human insulin (Exubera [EXU]) in 635 nonsmoking adults with type 2 diabetes.


METHODS
Patients were randomly assigned to receive prandial EXU or subcutaneous insulin (regular or short-acting) plus basal (intermediate- or long-acting) insulin. The primary end points were the annual rate of decline in forced expiratory volume in 1 s (FEV(1)) and carbon monoxide diffusing capacity (DL(CO)).


RESULTS
Small differences in FEV(1) favoring subcutaneous insulin developed during the first 3 months but did not progress. Adjusted treatment group differences in FEV(1) annual rate of change were -0.007 l/year (90% CI -0.021 to 0.006) between months 0 and 24 and 0.000 l/year (-0.016 to 0.016) during months 3-24. Treatment group differences in DL(CO) annual rate of change were not significant. Both groups sustained similar reductions in A1C by month 24 (last observation carried forward) (EXU 7.7-7.3% vs. subcutaneous insulin 7.8-7.3%). Reductions in fasting plasma glucose (FPG) were greater with EXU than with subcutaneous insulin (adjusted mean treatment difference -12.4 mg/dl [90% CI -19.7 to -5.0]). Incidence of hypoglycemia was comparable in both groups. Weight increased less with EXU than with subcutaneous insulin (-1.3 kg [-1.9 to -0.7]). Adverse events were comparable, except for a higher incidence of mild cough and dyspnea with EXU.


CONCLUSIONS
Two-year prandial EXU therapy showed a small nonprogressive difference in FEV(1) and comparable sustained A1C improvement but lower FPG levels and less weight gain than seen in association with subcutaneous insulin in adults with type 2 diabetes.
Rosenstock
Julio
J
Dallas Diabetes and Endocrine Center, Dallas, Texas, USA. juliorosenstock@dallasdiabetes.com
Cefalu
William T
WT
Hollander
Priscilla A
PA
Belanger
Andre
A
Eliaschewitz
Freddy G
FG
Gross
Jorge L
JL
Klioze
Solomon S
SS
St Aubin
Lisa B
LB
Foyt
Howard
H
Ogawa
Masayo
M
Duggan
William T
WT
D000280:Administration, Inhalation; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004058:Diffusion; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D044469:Racial Groups; D012129:Respiratory Function Tests; D012449:Safety; D016896:Treatment Outcome
D001786:Blood Glucose; C473734:Exubera; D007004:Hypoglycemic Agents; D007328:Insulin; D002248:Carbon Monoxide